bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2026–07–12
sixty-one papers selected by
Luca Bolliger, lxBio



  1. Int J Pharm. 2026 Jul 05. pii: S0378-5173(26)00603-4. [Epub ahead of print] 127155
      The rapid emergence of multidrug-resistant (MDR) bacteria has increased interest in bacteriophage therapy as a promising alternative to conventional antibiotics. Bacteriophages are host-specific bacterial viruses that selectively infect and destroy pathogenic bacterial strains. Recent developments in artificial intelligence (AI) and CRISPR-based technologies offer innovative approaches to address challenges such as narrow host range, rapid immune clearance, phage instability, bacterial resistance, and biofilm penetration barriers. By integrating AI-driven structural modeling with CRISPR-mediated genome editing, these methods enable the targeted delivery of bacteriophages. This review focuses on next-generation approaches that combine AI-assisted phage identification, host prediction, and therapeutic optimization with CRISPR-based genome engineering for targeted phage delivery and improved safety. Overall, this review highlights the potential of AI- and CRISPR-assisted phage therapy for the treatment of MDR bacterial infections. This review provides a systematic overview of bacteriophage biology, life cycle, and mechanisms of action, highlighting the influence of phage morphology on therapeutic performance, recent advances, current clinical and preclinical studies, and future perspectives. Although phage therapy shows considerable potential against MDR bacterial infections, several challenges related to delivery, safety, and clinical translation remain. The integration of AI and CRISPR technologies may improve phage selection, targeting specificity, and therapeutic performance. Continued research, clinical validation, and regulatory development will be essential for translating these advances into practical antimicrobial therapies.
    Keywords:  Artificial intelligence; Biofilms; CRISPR-Cas; Multidrug-resistant; Phage therapy; Precision medicine; Synthetic biology; Targeted delivery
    DOI:  https://doi.org/10.1016/j.ijpharm.2026.127155
  2. Cell Host Microbe. 2026 Jul 08. pii: S1931-3128(26)00273-8. [Epub ahead of print]34(7): 1285-1301
      There is growing interest in the development of bacteriophages as therapies for antimicrobial-resistant infections, but effective delivery of phages remains a barrier. This review examines the opportunities and challenges involved in the development of phages as drugs, focusing on phage delivery. We first review current practices and success rates for clinical phage therapy and recent advances in phage selection and design. Next, we frame ongoing delivery challenges in the context of what is known about phage biology and phage pharmacokinetics. We then explore barriers to effective phage delivery alongside dosing and administration strategies used to overcome them, followed by an examination of recent innovations in phage formulations and biomaterials technologies. Finally, we highlight outstanding questions and challenges in the field. We conclude that optimizing delivery is a key determinant of the success of phage therapy and that the integration of microbiology, materials science, and pharmacology will enable more consistent success.
    Keywords:  antimicrobial resistance; bacteria; bacteriophage therapy; delivery; phage; pharmacology
    DOI:  https://doi.org/10.1016/j.chom.2026.06.013
  3. Int J Vet Sci Med. 2026 ;14 9
      A 14-year-old American Quarter Horse mare developed a refractory deep surgical site infection following emergency celiotomy for acute right dorsal large colon displacement with 180° volvulus. Initial cultures revealed a high-burden polymicrobial infection with Escherichia coli and Enterococcus faecium, associated with delayed healing, and later followed by multidrug-resistant Pseudomonas aeruginosa, further limiting therapeutic options. Phage therapy was initiated using a customized lytic phage cocktail administered topically on a daily basis over a 35-day period, with cocktail composition guided by daily wound culture results. Phage therapy markedly reduced colony-forming units of targeted pathogens and promoted progressive healing. Wound microbial communities varied during treatment, demonstrating selective pathogen control while preventing residual populations from recolonizing the tissue. By the time of hospital discharge, the wound surface area had decreased by more than 85%, and the body wall had healed without evidence of acute herniation. This case highlights the feasibility, safety, and clinical potential of adaptive phage therapy for managing refractory multidrug-resistant equine wound infections.
    Keywords:  Celiotomy; Enterococcus faecium; Escherichia coli; Pseudomonas aeruginosa; equine wound infection; lytic phages; multidrug-resistant; phage therapy; surgical site infection
    DOI:  https://doi.org/10.4103/IJVSM.IJVSM_19_26
  4. Front Microbiol. 2026 ;17 1839739
      Acinetobacter baumannii poses a severe global health threat due to its extensive multi-drug resistance. This review explores the evolving role of phage therapy as a promising alternative against multi-drug resistant Acinetobacter baumannii infections. We reviewed the latest key mechanisms by which phages exert their therapeutic effects, including direct lysis, biofilm disruption via depolymerases, resensitization of resistant strains to antibiotics through receptor-mediated fitness trade-offs, and the action of phage-derived enzymes such as endolysins. Recent preclinical studies have demonstrated robust efficacy, while clinical case reports and ongoing trials highlight both the potential and challenges of compassionate phage use, including emergence of phage resistance and variable patient responses. Advances in pharmacokinetic optimization, including PEGylation to enhance circulation and immune evasion, are discussed alongside synergistic phage-antibiotic combinations and novel delivery systems such as hydrogel formulations for topical applications. The review further examines emerging strategies in phage engineering and synthetic biology aimed at overcoming host-range limitations and resistance development, including chimeric lysins with enhanced outer membrane penetration and photosensitizer-conjugated phages for biofilm eradication. Finally, we highlight emerging strategies in phage engineering and synthetic biology aimed at overcoming host-range limitations and resistance development, so as the role of artificial intelligence in cocktail design and personalized therapeutics.
    Keywords:  Acinetobacter baumannii; genetic engineering; mechanism; phage; therapy
    DOI:  https://doi.org/10.3389/fmicb.2026.1839739
  5. Int J Infect Dis. 2026 Jul 05. pii: S1201-9712(26)00601-6. [Epub ahead of print] 108966
       OBJECTIVES: Multidrug-resistant (MDR) Klebsiella pneumoniae is an increasingly important cause of recurrent urinary tract infections (UTIs). As bacteriophage therapy represents a promising alternative, we aimed to isolate and characterize bacteriophages targeting a clinical MDR K. pneumoniae strain causing recurrent UTI and evaluate their activity under urinary conditions.
    METHODS: Three bacteriophages targeting an ESBL-producing K. pneumoniae clinical isolate were obtained and characterized by genome sequencing, electron microscopy, stability assays, one-step growth curves, and host-range analysis across 79 UTI isolates. Phage activity was quantified in LB medium and human urine.
    RESULTS: Three lytic phages (EDIRA083, EDIRA088, and EDIRA092) belonging to distinct genera were identified. Absence of lysogeny-associated, virulence, or antibiotic-resistance genes was confirmed. Capsule, LPS and maltoporin LamB were identified as receptors for EDIRA083 and EDIRA092. Host-range analysis revealed narrow activity for EDIRA083 and EDIRA088, whereas EDIRA092 infected 29% of the panel strains. In liquid phage infection assays, overall lytic activity was consistently higher and more sustained in human urine than in LB.
    CONCLUSIONS: These results identify three genetically distinct lytic phages targeting MDR K. pneumoniae. Their activity in urine supports further evaluation of these phages as candidates for therapeutic development against MDR Klebsiella UTI.
    Keywords:  Klebsiella pneumoniae; bacteriophage; multidrug resistance; phage therapy; urinary tract infection
    DOI:  https://doi.org/10.1016/j.ijid.2026.108966
  6. Front Vet Sci. 2026 ;13 1829777
      Antimicrobial resistance (AMR) in animal production systems is a major structural driver of the global resistance crisis. Food-producing animals account for the majority of global antimicrobial consumption, generating sustained selective pressure across livestock, environmental, and zoonotic bacterial reservoirs. Intensive poultry, swine, cattle, and aquaculture systems amplify pathogen transmission and accelerate resistance emergence. Bacteriophage therapy offers a species-specific, microbiome-preserving alternative to conventional antibiotics; however, large-scale veterinary implementation has historically been constrained by challenges including strain-level host prediction, resistance evolution, biosafety considerations, manufacturing scalability, economic feasibility, and regulatory adaptation. Recent advances in artificial intelligence (AI) show promise for enabling precision veterinary phage therapy, though most applications remain at the computational proof-of-concept or preclinical stage. Deep learning and graph-based genomic models have demonstrated high accuracy on benchmark datasets, reinforcement learning has been explored in computational models for cocktail optimization, and AI-assisted genomic screening can enhance biosafety assessment. Integration with real-time AMR surveillance could potentially facilitate adaptive deployment strategies, subject to field validation. Economic modeling suggests that moderate reductions in metaphylactic antibiotic use could yield production and public health benefits, though these estimates remain illustrative. This review synthesizes current evidence on AI-guided phage discovery, epidemiological modeling, microbiome modulation, horizontal gene transfer risk assessment, economic evaluation, and regulatory innovation. Within a One Health framework, adaptive AI-guided phage platforms represent a high-leverage strategy for reducing antimicrobial dependence, provided that critical knowledge gaps are addressed.
    Keywords:  One Health; antimicrobial resistance; artificial intelligence; bacteriophage therapy; evolutionary modeling; livestock production; phage–host interaction; precision livestock farming
    DOI:  https://doi.org/10.3389/fvets.2026.1829777
  7. Ther Deliv. 2026 Jul 09. 1-18
      Diabetic foot ulcers (DFUs) are serious complications of diabetes, and consist of chronic wound healing, chronic biofilm infection, impaired angiogenesis, oxidized stress, and persistent inflammation. Standard treatments such as systemic antibiotics and growth factors have been found to be ineffective due to poor tissue penetration, degradation and antimicrobial resistance. The aim of this review is to critically analyze advanced strategies for combination therapy using antibiotics, growth factors and/or nanocarriers in order to better manage DFU. Literature was searched in PubMed, Scopus, Web of Science, and Google Scholar databases from January 2010 to March 2026 using keywords related to DFUs, antibiotics, growth factors, nanocarriers, biofilms, and wound healing. Combination nanotherapeutic systems exhibited potential to improve local drug delivery, disrupt biofilms, promote angiogenesis and support tissue regeneration. Stimuli-responsive and sequential-release platforms could enhance therapeutic precision by synchronizing antimicrobial and regenerative functions. Controlled release and modulation of the wound microenvironment are also enhanced by engineering scaffolds and multifunctional biomaterials. Yet the hurdles of biosafety, oxidative cytotoxicity, manufacturing scale-up, regulatory approval, and extended clinical duration remain significant obstacles to translation. Advanced multifunctional nanotherapeutics represent promising emerging strategies for precision-based DFU treatment and may improve infection control, tissue regeneration, and clinical healing outcomes.
    Keywords:  Diabetic foot ulcers (DFUs); biofilm-associated infections; combination therapy; growth factor; nanocarrier drug delivery; stimuli-responsive nanomaterials
    DOI:  https://doi.org/10.1080/20415990.2026.2699574
  8. Bioinformatics. 2026 Jul 01. pii: btag262. [Epub ahead of print]42(Supplement_1):
       MOTIVATION: Bacteriophages (phages) are key regulators of bacterial populations and hold great promise for applications such as phage therapy, biocontrol, and industrial fermentation. The success of these applications depends on accurately determining phage host range, which is often specific at the strain level rather than the species level. However, existing computational approaches face major limitations: many rely on genus-specific features that do not generalize across taxa, while others require large amounts of training data that are unavailable for most bacterial lineages. These challenges create a critical need for methods that can accurately predict strain-level phage-host interactions across diverse bacterial genera, particularly under data-limited conditions.
    RESULTS: We present PhageMind, a learning framework designed to address this challenge by enabling efficient transfer of knowledge across bacterial genera. PhageMind is trained to identify shared principles of phage-bacterium interactions from well-studied systems and to rapidly adapt these principles to new genera using only a small number of known interactions. To reflect the biological basis of infection, we represent phage-host relationships using a knowledge graph that explicitly incorporates phage tail fiber proteins and bacterial O-antigen biosynthesis gene clusters, and we use this representation to guide interaction prediction. Across four bacterial genera (Escherichia, Klebsiella, Vibrio, and Alteromonas), PhageMind achieves high prediction accuracy and shows strong adaptability to new lineages. In particular, in leave-one-genus-out evaluations, the model maintains robust performance when only limited reference data are available, demonstrating its potential as a scalable and practical tool for studying phage-host interactions across the global phageome.
    AVAILABILITY AND IMPLEMENTATION: The source code of PhageMind is available via: https://github.com/YangSH-ac/PhageMind.
    DOI:  https://doi.org/10.1093/bioinformatics/btag262
  9. Front Biosci (Elite Ed). 2026 Jun 01. 18(2): 44070
      Since the discovery of penicillin in 1928, more than a thousand antibiotics have been introduced into medical practice. Initially, the introduction of antibiotics revolutionized the treatment of infectious diseases. However, as antibiotics have been used repeatedly, scientists and clinicians have observed serious adverse consequences, most notably the emergence of bacterial resistance to antimicrobial agents. Of particular concern are multidrug-resistant pathogens, which are resistant to multiple antibiotic classes. As of 2024, antibiotic-resistant bacteria are directly responsible for approximately 1.27 million deaths worldwide. Thus, in response, possible new antibacterial agents are under investigation, including bacteriophages and the associated bacteriolytic enzymes. According to the World Health Organization (WHO), phage-based drugs are leading nonclassical antibiotics currently in clinical trials. Meanwhile, endolysins, as bacteriolytic phage enzymes, have emerged as promising antibacterial agents. This study reviews the key achievements and mechanisms of action of bacteriophage endolysins against bacterial infections, including biofilms, and discusses the therapeutic potential of endolysins in combating antibiotic resistance. Finally, the combined use of endolysins with other biomolecules and the application of artificial intelligence to address antimicrobial-resistant infections are also discussed.
    Keywords:  bacteriophages; endolysins; infection; multidrug resistance; therapy
    DOI:  https://doi.org/10.31083/FBE44070
  10. J Assoc Med Microbiol Infect Dis Can. 2026 Jun;11(2): 215-223
       Background: Prosthetic joint infections (PJIs) pose a significant treatment challenge due to biofilm-associated resistance, which limits antibiotic effectiveness. Bacteriophages, naturally occurring viruses that selectively infect and lyse bacteria, can disrupt biofilms, potentially enhancing antibiotic activity. We present the case of a male in his 70s with a history of total hip arthroplasty in 1973 who developed a chronic methicillin-susceptible Staphylococcus aureus (MSSA) PJI. Despite eight surgical interventions and multiple courses of suppressive antibiotics, the infection persisted, necessitating the use of bacteriophage therapy.
    Methods: The patient's MSSA isolate was sent to a bacteriophage laboratory in Quebec, which identified effective bacteriophages, and a two-bacteriophage cocktail was selected. Following approval by Health Canada and the University of Calgary (REB23-1733), bacteriophages were administered during a planned incision and drainage (I&D). Locally, bacteriophage was applied topically into the hip, followed by 2 weeks of twice-daily intravenous bacteriophage therapy with standard-of-care intravenous antibiotics.
    Results: Therapy was well tolerated except for initial mild rigors. Now, 24 weeks after bacteriophage administration, there is cessation of pain, normalization of inflammatory markers, and significant improvement in quality of life while continuing on suppressive antibiotics.
    Conclusions: Bacteriophage therapy was safe in our case, and emerging evidence is promising for its use in PJIs. However, regulatory hurdles, cost, and lack of standardized protocols currently limit its use. Classified as experimental therapy in Canada, bacteriophage use is restricted to clinical trials. This case underscores the potential for broader adoption of bacteriophage therapy in managing PJIs across Canada.
    Keywords:  antibiotic; infection; joint; phage; prosthetic joint infection; therapy
    DOI:  https://doi.org/10.3138/jammi-2025-0015
  11. Folia Microbiol (Praha). 2026 Jul 09.
      Antimicrobial resistance (AMR) represents one of the most critical healthcare concerns worldwide, specifically amplified by the ESKAPE pathogens, which represent the six most nosocomial pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species. The ESKAPE pathogens pose a crucial challenge due to their unique ability to acquire resistance to most of the currently available drugs. Globally, a serious and alarming prevalence trajectory of ESKAPE pathogens has been seen, responsible for healthcare-associated infections, such as urinary tract infection (UTI) and ventilator-associated pneumonia (VAP). These infections are considered one of the major contributors to morbidity and mortality rates worldwide. This review highlights an emerging trend of AMR associated with UTI and VAP in hospital settings. Furthermore, this review discusses the key mediators of host immune response against ESKAPE pathogens involved in causing UTI and VAP. Developing specific therapeutics and enhancing antimicrobial stewardship strategies against these pathogens may contribute to curbing the growing menace of AMR.
    Keywords:  AMR; ESKAPE pathogens; immune response; nosocomial infection; virulence factors
    DOI:  https://doi.org/10.1007/s12223-026-01549-4
  12. Polim Med. 2026 Jan-Jun;56(1):56(1): 41-51
      This article aims to present the current state of knowledge on four major biotechnological antimicrobial strategies and to evaluate their potential clinical applications in the context of increasing antibiotic resistance. Approaches such as phage therapy, CRISPR-Cas9 gene editing, nanoparticles, and antimicrobial peptides (AMPs) may significantly contribute to limiting the spread of resistance genes. Particular attention is given to advances in genetic engineering that enable precise targeting and elimination of resistance determinants, as well as to the therapeutic potential of the microbiome. A literature review of studies published between 2010 and 2025 was conducted using the following keywords: antimicrobial resistance, phage therapy, CRISPR-Cas9, AMPs, and nanotechnology. Both review articles and original studies, including preclinical and clinical data, were considered. Phage therapy demonstrates high efficacy against antibiotic-resistant pathogens, particularly in the form of phage cocktails and genetically engineered phages. Antimicrobial peptides exhibit broad-spectrum activity and can be structurally optimized to improve stability and selectivity. CRISPR-Cas9 systems enable targeted elimination of resistance genes or direct disruption of pathogen genomes, while nanotechnology facilitates drug delivery, biofilm penetration, and bactericidal activity, particularly through metal-based nanoparticles. Notably, all approaches show potential for synergistic use with conventional antibiotics. Biotechnological treatment strategies may become a key component in combating antibiotic resistance. However, their clinical implementation requires further research, comprehensive safety evaluation, regulatory development, and integration into medical practice. Advances in these areas could significantly reduce the global burden of infectious diseases.
    Keywords:  CRISPR-Cas9; antimicrobial peptides; antimicrobial resistance; nanotechnology; phage therapy
    DOI:  https://doi.org/10.17219/pim/218777
  13. Access Microbiol. 2026 ;pii: 001158.v3. [Epub ahead of print]8(7):
      Phages are viruses that infect bacteria and have therapeutic potential due to their ability to selectively kill bacterial pathogens. Despite growing scientific and policy interest in phage therapy, public and professional understanding of phages remains limited, posing a barrier to wider clinical adoption. Here, we present the development and evaluation of open-source, 3D-printed microbial models designed to communicate core concepts in phage biology, including phage diversity, host specificity and life cycle differences between virulent and temperate phages. These tactile, compact models were tested across multiple public engagement events with diverse audiences. Survey data showed high usability and educational value, 90% of participants reported improved understanding of phage-bacteria interactions, and many expressed interest in learning more. Thematic analysis of qualitative feedback highlighted sustained engagement and prompted iterative model refinements to improve clarity and accessibility. These models offer a low-cost, scalable tool to support outreach and education around phage biology, including its applications in treating drug-resistant infections. By bridging the gap between complex scientific concepts and public understanding, they contribute to broader efforts to build awareness of phage-based alternatives to traditional antibiotics.
    Keywords:  3D printing; active learning; bacteriophages; creative science communication; education; public engagement
    DOI:  https://doi.org/10.1099/acmi.0.001158.v3
  14. Biotechnol Bioeng. 2026 Jul 05.
      Pseudomonas aeruginosa (P. aeruginosa) is a leading cause of urinary tract infections (UTIs). The escalating misuse of antibiotics has led to the emergence of multidrug-resistant strains, necessitating novel therapeutic approaches. Bacteriophages and their encoded lytic enzymes offer unique advantages for antimicrobial therapy and show promising potential for future applications. This study focuses on the characterization of uropathogenic P. aeruginosa phages and their lytic enzymes, investigating their biological properties and potential therapeutic applications. We isolated a novel lytic bacteriophage, vB_PaeS_PA16c (PPA16c), which demonstrated favorable biological characteristics, including a 34% biofilm eradication capacity within 6 h. The phage-encoded endolysin PA16cLys exhibited superior antibacterial efficacy compared to the phage itself. Notably, it achieved significant biofilm reduction (~63%) after 1 h treatment without requiring outer membrane permeabilizers. This endolysin exhibited enhanced antibacterial efficacy in eradicating mature P. aeruginosa biofilms. Regarding host range, PA16cLys displayed broader lytic activity. Both the phage and endolysin demonstrated cross-order lytic activity against other pathogenic bacteria. Crucially, PA16cLys maintained potent inhibitory activity against phage-resistant mutants. These findings provide a theoretical foundation for utilizing phages and lytic enzymes against uropathogenic P. aeruginosa and establish a research basis for developing novel antimicrobial therapy.
    Keywords:  Pseudomonas aeruginosa; bacteriophage; endolysin; urinary tract infection
    DOI:  https://doi.org/10.1002/bit.70301
  15. Biomol Concepts. 2026 Jan 01. 17(1):
      Since their discovery, bacteriophages - viruses that infect bacteria - have fascinated scientists due to their ubiquity and potential applications in fields ranging from molecular biology to biotechnology and medicine. However, in fermentation processes that depend on bacterial activity, bacteriophages can pose a major threat by infecting and disrupting key microbial populations, leading to delayed or failed fermentations and resulting in economic losses. While the impact of bacteriophages on fermented dairy foods, such as yogurt and cheese, is well-documented, such knowledge is comparatively limited for fermented soybean foods (FSFs). Most FSFs (such as Cheonggukjang, Miso, Thua Nao, and soy sauce) are traditionally produced using natural microbiota under less controlled conditions. This makes them more susceptible to unpredictable microbial dynamics, including phage interference. In this review, we examine the diversity and occurrence of bacteriophages associated with FSFs. Finally, the potential roles of bacteriophages in FSFs - ranging from fermentation disruption to possible microbial modulation - are also discussed.
    Keywords:   Bacillus ; bacteriophage; fermented soybean
    DOI:  https://doi.org/10.1515/bmc-2025-0061
  16. Eur J Clin Microbiol Infect Dis. 2026 Jul 06.
       PURPOSE: Carbapenem-resistant Acinetobacter baumannii (CRAB) represents a critical global health threat for which existing antibiotics are increasingly inadequate. This study aimed to establish a comprehensive genomic framework for the rational prioritization of virulent Acinetobacter bacteriophages as therapeutic candidates.
    METHODS: We performed large-scale comparative genomic analysis of 340 virulent Acinetobacter bacteriophages, integrating phylogenetic reconstruction, pangenome analysis, CRISPR spacer-based host interaction mapping, Anti-CRISPR protein identification, and systematic antimicrobial resistance (AMR) gene screening.
    RESULTS: Genome sizes spanned a nearly 20-fold range, with a significant negative correlation between genome size and GC content (R² = 0.139, ρ = -0.630). Phylogenetic analysis revealed extensive divergence across multiple lineages with no dominant clade. Pangenome analysis identified 20,982 unique protein families, of which 76.2% were cloud genes, confirming a highly open genome architecture. CRISPR spacer matching yielded 1,480 high-confidence matches across 100 phage genomes, providing molecular evidence of broad historical infectivity. Anti-CRISPR profiling identified Acinetobacter phage XC1 as an exceptional therapeutic candidate harboring 55 predicted Anti-CRISPR proteins with canonical regulatory locus architecture. AMR screening identified 21 distinct AMR gene homologs (Loose RGI hits, 22.5 to 47.1% amino acid identity) distributed heterogeneously across the dataset, confirming abundant therapeutically clean candidates while flagging a subset warranting further scrutiny before therapeutic exclusion.
    CONCLUSION: These findings provide a multi-criteria genomic framework for rational phage candidate prioritization against multidrug-resistant Acinetobacter infections, with direct implications for evidence-based phage therapy development.
    Keywords:   Acinetobacter baumannii ; Anti-CRISPR; Antimicrobial resistance; CRISPR spacer; Carbapenem resistance; Phage therapy
    DOI:  https://doi.org/10.1007/s10096-026-05580-8
  17. Mol Biol Rep. 2026 Jul 10. pii: 1135. [Epub ahead of print]53(1):
       BACKGROUND: Antimicrobial resistance has renewed interest in Phage therapy as an alternative or adjunct to antibiotics. However, immune responses to repeated phage exposure may influence treatment outcomes, and the impact of the route of administration on these responses remains incompletely understood. This study evaluated humoral and cytokine responses following repeated administration of a lytic phage cocktail in healthy rats through different parenteral routes.
    METHODS: A cocktail of four lytic phages targeting multidrug-resistant Klebsiella pneumoniae was administered repeatedly to healthy rats via the intraperitoneal (IP), intramuscular (IM), intravenous (IV), and subcutaneous (SC) routes. Humoral responses were assessed by measuring anti-phage immunoglobulins (IgM, IgG, and IgA) and neutralising antibodies, while systemic cytokines (TNF-α, IL-1β, IL-6, and IL-10) were quantified.
    RESULTS: Repeated phage administration elicited route-dependent humoral immune responses. Neutralising antibody levels peaked by day 14 in the IP, IM, and IV groups, reflecting early IgM responses. A second peak occurred after the seventh dose, administered 37 days later. The IP route triggered the strongest and sustained antibody response, particularly IgG, whereas responses following SC administration were weaker and delayed. IgA levels remained low across all routes. Cytokine analysis revealed only mild, transient fluctuations in TNF-α, IL-1β, IL-6, and IL-10, with no evidence of sustained systemic inflammatory activation. The observed cytokine profile warrants further investigation to determine whether the phage cocktail exerts anti-inflammatory effects.
    CONCLUSIONS: Phage-induced immune responses may be route-dependent and complex. These findings enhance our understanding of host-phage interactions and underscore the need for further pharmacokinetic and immunological studies to assess their relevance to phage therapy.
    Keywords:  Anti-inflammatory; Antibodies; Cytokine; Immunology; Multidrug-resistant; Neutralizing
    DOI:  https://doi.org/10.1007/s11033-026-12330-8
  18. Folia Microbiol (Praha). 2026 Jul 06.
      Salmonella Enteritidis is a major causative agent of gastroenteritis and foodborne illnesses, posing significant therapeutic challenges due to the rise of multidrug-resistant (MDR) strains. The increasing prevalence of resistant isolates highlights the need for alternative strategies to improve treatment outcomes. Lytic bacteriophage therapy has emerged as a promising complementary approach to antimicrobials. This study aimed to investigate the synergistic bacteriostatic and bactericidal effects of a newly formulated cocktail comprising three distinct lytic bacteriophages combined with selected antimicrobials against the standard strain of Salmonella Enteritidis (ATCC 13076). Three distinct bacteriophages were isolated from poultry farm wastewater, purified based on their different plaque morphologies, and characterized by transmission electron microscopy (TEM), revealing short non-contractile tailed caudoviruses. Phage stability was evaluated across a pH range of 3 to 11 and temperatures from 4 to 50 °C. The minimum inhibitory concentration (MIC) was determined using the macrodilution (tube dilution) method, and viable bacterial counts (CFU/mL) were measured at 0, 6, 12, and 24 h to assess the bacteriostatic and bactericidal effects on the bacterial strain. The phage cocktail combined with ciprofloxacin and ceftriaxone showed significant synergistic activity, resulting in reductions of 5.8 and 4.9 log CFU/mL, respectively, corresponding to up to a 75% reduction in MIC. In contrast, combinations with ampicillin and erythromycin demonstrated the least efficacy. The phage cocktail alone achieved a 3.2 log reduction in CFU/mL. The phage cocktail demonstrated enhanced antibacterial activity when combined with ciprofloxacin or ceftriaxone, achieving greater reductions in Salmonella Enteritidis counts compared to individual treatments. Minimal synergy was observed with ampicillin and erythromycin. Overall, the evaluated phage-antimicrobial combinations exhibited superior antibacterial effects within the scope of this study.
    Keywords:   Salmonella Enteritidis; Antimicrobial; Bacteriophage; Phage cocktail; Synergy
    DOI:  https://doi.org/10.1007/s12223-026-01534-x
  19. Cureus. 2026 Jun;18(6): e110562
       BACKGROUND: Periodontitis and liver cirrhosis are chronic inflammatory disorders characterized by dysregulated immune responses and an increased systemic inflammatory load. Neutrophil gelatinase-associated lipocalin (NGAL) is a neutrophil-derived biomarker implicated in inflammation, tissue injury, and systemic disease. The relationship between salivary NGAL and periodontal health has not been previously studied in individuals with liver cirrhosis.
    AIM: To evaluate and compare salivary NGAL levels among patients with liver cirrhosis with and without periodontitis, periodontitis alone, and healthy controls.
    MATERIALS AND METHODS: This cross-sectional study included 40 participants divided into four groups (n=10 each): liver cirrhosis with periodontitis, liver cirrhosis only, periodontitis only, and healthy controls. Periodontal status was evaluated using standardized clinical parameters in accordance with the 2017 American Academy of Periodontology (AAP) classification criteria. Unstimulated whole saliva samples were obtained, and salivary NGAL concentrations were quantified using enzyme-linked immunosorbent assay (ELISA). Intergroup comparisons were analyzed using one-way analysis of variance (ANOVA).
    RESULTS: Salivary NGAL levels differed significantly among the study groups (p<0.001). The highest NGAL levels were observed in patients with liver cirrhosis and periodontitis, followed by liver cirrhosis alone, periodontitis alone, and healthy controls. These findings indicate an additive inflammatory effect when periodontal disease coexists with liver cirrhosis.
    CONCLUSION: Salivary neutrophil gelatinase-associated lipocalin (NGAL) levels were significantly increased in patients presenting with both liver cirrhosis and periodontitis, indicating an enhanced cumulative systemic and periodontal inflammatory burden. Salivary NGAL may serve as a potential non-invasive biomarker linking periodontal inflammation and liver disease. Further longitudinal investigations involving larger sample populations are required to substantiate its clinical applicability and diagnostic utility.
    Keywords:  biomarker; liver cirrhosis; neutrophil gelatinase-associated lipocalin; oral–systemic link; periodontitis; saliva
    DOI:  https://doi.org/10.7759/cureus.110562
  20. Int J Antimicrob Agents. 2026 Jul 06. pii: S0924-8579(26)00200-1. [Epub ahead of print] 107913
       OBJECTIVE: Limiting the emergence of phage resistance is a key priority in optimizing phage therapy. However, it remains poorly understood whether the development of antibiotic resistance influences the evolution of phage resistance.
    METHODS: To investigate phage-host interactions, we used both colistin resistant strains derived from the wild-type and genetically engineered knockout mutants. Transcriptomic analysis was employed to examine the adaptive responses of these colistin-resistant mutants under phage pressure. Finally, we characterized the phage-resistant variants that evolved in the colistin-resistant backgrounds.
    RESULTS: Our results demonstrate that the emergence of phage-resistant variants was significantly reduced in colistin resistant mutants. These phenotypic changes were primarily mediated by disruption of lpxC and lpxD, with additional effects from compensatory mutations and amino acid metabolism. The ΔlpxC and ΔlpxD mutants exhibited distinct transcriptional profiles and metabolic features under phage pressure. The astA-mediated arginine metabolism pathway was a key modulator of phage-colistin-resistant mutant interactions. In the ΔlpxD background, Mla system inactivation and arginine supplementation accelerated the phage resistance evolution (including via the mucoid phenotype). Capsule defects arising during phage resistance development in both ΔlpxC and ΔlpxD mutants simultaneously increased colistin susceptibility.
    CONCLUSIONS: Overall, lpxC/lpxD disruption constrains phage resistance evolution in A. baumannii. Compensatory mutation and bacterial metabolism not only mitigate fitness cost and maintain antimicrobial resistance but also expand evolutionary trajectories of bacteria under phage pressure. These findings reveal the adaptive mechanisms of colistin-resistant A. baumannii under phage selection and support the optimization of phage therapy.
    Keywords:  Acinetobacter baumannii; Mla system; arginine metabolism; colistin resistance; phage resistance
    DOI:  https://doi.org/10.1016/j.ijantimicag.2026.107913
  21. Compend Contin Educ Dent. 2026 Jul-Aug;47(5):47(5): 241-243
      Increasing evidence suggests chronic periodontal inflammation may contribute to systemic inflammatory burden, including in medically compromised patients. Studies have demonstrated associations between moderate to advanced periodontitis and numerous chronic medical systemic conditions. As interdisciplinary treatment models become more common, oral health evaluation and periodontal stabilization are emerging as important components of pretreatment medical optimization. This article reviews the relationship between periodontal inflammation and systemic disease, examines current treatment approaches and diagnostic technologies, and presents a multidisciplinary clinical workflow in which medical and dental professionals collaborate to reduce oral inflammatory burden prior to a major medical intervention.
  22. Int J Microbiol. 2026 ;2026 4451708
       Background: Recently, bacteriophages have risen as a potent therapy for superbug infections. The mammal gut demonstrates an interesting source of virulence bacteriophages. The gut with inflammation is phage-rich; therefore, we primarily aimed to prove the concept that an inflammatory gut is a possible source of effective phages and to evaluate the efficacy of the candidate phage against Pseudomonas aeruginosa in vitro and in a mouse model of infected wounds.
    Results: The gut microbiome of cecal ligation and puncture (CLP) sepsis mice, an animal model of inflammation, showed a dominant presence of Podoviruses. CLP bacteriophages (CLP Φ1-Φ4), of which the CLP Φ4 possessed the broadest bactericidal activity (viable bacterial cell reduction in time-kill study) against P. aeruginosa isolates. The CLP Φ4 specifically killed the Pseudomonas aeruginosa clinical (PACL) strain with two huge burst events. Although the CLP Φ4 had no effect on ex vivo mouse bone marrow-derived macrophage (BMDM) cytokine gene expression and cytokine production, the CLP Φ4 attenuated the severity of the P. aeruginosa-infected wound mouse model after treatment. P. aeruginosa PACL exhibited significantly pathogenic characteristics in a mouse model, including excessive bacterial loads (in wounds and internal organs, indicating the systemic infection due to localized infected wound with P. aeruginosa), increased IL-6 cytokine (in serum), upregulated IL-6 expression (in wounds), and immune cell infiltration (in wounds), indicating severe inflammation. In the CLP Φ4 treatment alone, the wound tissues upregulated IL-10 expression and recruited inflammatory cells. Interestingly, the three-day CLP Φ4 treatment was adequate to eradicate P. aeruginosa PACL in the wounds and other internal organs. After treatment, the mouse serum cytokine showed a remarkably decreased IL-6. Likewise, IL-6 downregulation and IL-10 upregulation were demonstrated in the treated wounds, suggesting an anti-inflammatory shift. These results demonstrated the effectiveness (bacterial wound and internal organ clearance and cytokine modulation) of the CLP Φ4 in the P. aeruginosa-infected wound and systemic infection. Finally, the CLP Φ4 isolation verified a proof of concept that the irritated gut acts as a source of bacteriophages.
    Conclusions: The gut virome was a promising and interesting source of antimicrobial and immunomodulating bacteriophage.
    Keywords:  Pseudomonas aeruginosa; Pseudomonas aeruginosa-infected wound model; bacteriophage; bacteriophage therapy; cecal ligation and puncture (CLP) model; wound infection
    DOI:  https://doi.org/10.1155/ijm/4451708
  23. Microbiol Res. 2026 Jul 08. pii: S0944-5013(26)00184-9. [Epub ahead of print]312 128620
       BACKGROUND: Staphylococcus aureus (S. aureus) is a key pathogen involved in chronic suppurative otitis media (CSOM). Antibiotic resistance and biofilm formation complicate CSOM treatment. Therefore, alternative therapies are urgently needed. Bacteriophage therapy, which specifically targets and destroys methicillin-resistant S. aureus (MRSA) and degrades biofilms, presents a promising option.
    METHODS: In this study, a lytic bacteriophage targeting S. aureus was isolated and named JD929. Its biological properties were analyzed, including its stability across different pH levels and temperatures, host range, and growth kinetics. Whole-genome sequencing and bioinformatics analyses were performed for taxonomic classification. Additionally, structural prediction and homology analysis of the tail protein (ORF8) were conducted using AlphaFold. The antibiofilm activity of JD929 against CSOM-associated S. aureus was also assessed.
    RESULTS: JD929 demonstrated high stability across a broad range of pH levels and temperatures and exhibited a distinct host spectrum from that of phage SLPW. One-step growth analysis showed a latent period of 30 min and a burst size of 156 PFU per cell. Genomic analysis identified JD929 as a member of the Rountreeviridae family. Structural prediction revealed that the tail protein has unique sequence and structural features, indicating a potential role in host recognition. Functionally, JD929 significantly inhibited biofilm formation and disrupted mature biofilms of CSOM-associated S. aureus.
    CONCLUSIONS: The newly isolated bacteriophage JD929 exhibits beneficial biological properties and strong, strain-specific antibiofilm activity, highlighting its potential as an alternative treatment for CSOM-associated S. aureus infections.
    Keywords:  Antibiofilm activity; Antibiotic resistance; Biofilm; Phage; Phage therapy; S. aureus
    DOI:  https://doi.org/10.1016/j.micres.2026.128620
  24. Immunotherapy. 2026 Jul 06. 1-28
      The skin microbiome is a complex and dynamic ecosystem that plays a pivotal role in maintaining skin barrier integrity and immune homeostasis. This review provides a comprehensive synthesis of current knowledge on the composition, diversity, and functional significance of the skin microbiota, with particular emphasis on site-specific and temporal variations, as well as intrinsic and extrinsic factors influencing microbial balance. Relevant literature was identified through comprehensive searches of PubMed, Scopus, Web of Science, and Google Scholar databases covering publications from 2018 to 2026. We discuss the multilayered architecture of the skin barrier, encompassing chemical, physical, microbial, and adaptive immune components, and highlight how commensal microorganisms contribute to barrier maintenance, lipid homeostasis, immune modulation, and colonization resistance against pathogens. Dysbiosis of the skin microbiome is critically examined in common dermatological disorders, including wound infections, atopic dermatitis, acne, and psoriasis, where microbial imbalance is closely linked to inflammation and disease progression. This review further explores emerging microbiome-targeted therapeutic strategies aimed at restoring microbial equilibrium and strengthening skin barrier function. Emerging therapies including bacteriotherapy, probiotics, phage therapy, and microbiome transplantation show promise, while challenges involving safety, ethics, and clinical translation remain important considerations.
    Keywords:  Microbiome; bacteriotherapy; dermatological disorders; immune modulation; live biotherapeutics
    DOI:  https://doi.org/10.1080/1750743X.2026.2697682
  25. Clin Transl Med. 2026 Jul;16(7): e70723
       BACKGROUND: Oral squamous cell carcinoma (OSCC) remains a major clinical challenge, with delayed diagnosis, frequent resistance to therapy, and poor long-term survival.
    METHODS: This review systematically evaluates the methodological framework for applying AI to oral microbiome data in OSCC. Emerging paradigms, including self-supervised learning for leveraging unlabelled data and explainable AI (XAI) techniques for model interpretability, are also discussed. Model evaluation relies on cross-validation, hyperparameter optimisation, and performance metrics such as AUC, accuracy, sensitivity, specificity, and F1-score.
    RESULTS: Multiple studies demonstrate that AI-based classifiers, especially random forest models built on salivary or tissue-derived microbial features, achieve outstanding discrimination between OSCC patients and healthy controls in retrospective, single-centre cohorts, with reported AUC values exceeding 0.99 and accuracy >95%. However, these exceptional metrics should be interpreted with caution, as they are susceptible to cohort size, sampling site heterogeneity, batch effects, feature-selection bias, and the absence of independent external validation. Beyond binary diagnosis, AI has been successfully applied to predict lymph node metastasis, explore tumour metabolic reprogramming, and assess environmental interactions. Integrated multi-omics approaches further enhance the specificity and clinical relevance of microbial biomarkers.
    CONCLUSIONS: The convergence of AI and oral microbiome analysis is reshaping the diagnostic and therapeutic landscape of OSCC, and explore microbiome-targeted combination therapies. Addressing these challenges will be pivotal to realising truly intelligent, personalised management and ultimately improving outcomes for OSCC patients.
    Keywords:  artificial intelligence; diagnosis; machine learning; oral microbiome; oral squamous cell carcinoma (OSCC); prognosis; tumour microenvironment
    DOI:  https://doi.org/10.1002/ctm2.70723
  26. Methods Mol Biol. 2026 ;3030 213-226
      Proteins are central to nearly all biological processes, mediating enzymatic catalysis, structural scaffolding, and molecular signaling. Deciphering how linear amino acid sequences encode three-dimensional conformations and biological functions has long been a defining challenge in molecular life sciences. Traditional structural biology approaches, such as X-ray crystallography and cryo-electron microscopy, have established the field, yet their high cost, labor intensity, and limited throughput restrict comprehensive coverage of the proteome. The exponential expansion of protein sequence databases, paired with advances in artificial intelligence (AI) and deep learning, has drastically accelerated our ability to predict, annotate, and even design proteins. In this mini review, we trace the evolution of AI-driven methods in protein research, from early residue-contact prediction using coevolutionary information to transformative breakthroughs, the rise of protein language models (PLMs), and the emerging era of generative design and functional modeling. Throughout, we highlight key conceptual advances and their translational implications for biomedical science and biotechnology.
    Keywords:  Artificial intelligence; Generative design; Molecular docking; Protein language model; Protein structure prediction
    DOI:  https://doi.org/10.1007/978-1-0716-5249-7_13
  27. Front Microbiol. 2026 ;17 1845440
      Bacteriophages are ubiquitous in nature, but relatively few have been isolated and characterized compared to the number of bacterial strains. Phage biotechnology applications benefit from a diverse library of isolated phages to kill or transfer genetic material to a bacterium of interest. However, scaling up phage discovery for diverse bacterial hosts can be time-consuming and costly. We developed an approach to capture novel phages for multiple bacterial strains in parallel from an environmental sample using commercially available 0.2-μM filter plates. Using this High-throughput Phage Isolation Platform (HtPIP), 12 novel phages were isolated spanning 9 diverse bacterial host genera. Eleven of the isolated phages define new phage species, with nine also defining new genera. The HtPIP was used to discover both DNA and RNA phages, including a Tectiviridae infecting Pseudomonas putida mt-2 and a Leviviricetes infecting a Microbacterium isolate, which represents the first cultured RNA phage infecting a host outside of Proteobacteria. Using a metagenomic approach, we demonstrate that the HtPIP captures a higher proportion of novel phages compared to traditional low-throughput methods.
    Keywords:  high-throughput; phage discovery; phage diversity; phage genome; phages
    DOI:  https://doi.org/10.3389/fmicb.2026.1845440
  28. J Int Med Res. 2026 Jul;54(7): 3000605261458669
      Chronic obstructive pulmonary disease is a prevalent chronic respiratory disorder that often coexists with multidrug-resistant bacterial infections in the lungs, significantly increasing treatment complexity and patient mortality. Consequently, research on the prevention and management of chronic obstructive pulmonary disease complicated by pulmonary multidrug-resistant bacterial infections has attracted increasing attention. Establishing predictive models for chronic obstructive pulmonary disease complicated by multidrug-resistant bacterial infections based on clinical risk factors has become a crucial direction in current clinical research. This narrative review summarizes the limitations of currently available predictive models, particularly in the selection of major risk factors and model construction. It aims to provide guidance for the selection and optimization of future predictive model development methods. The goal is to enhance the predictive performance and clinical applicability of these models while laying a theoretical foundation for the transformation of diagnostic and therapeutic paradigms.
    Keywords:  Chronic obstructive pulmonary disease; multidrug-resistant bacteria; prediction models; pulmonary infection; risk factors
    DOI:  https://doi.org/10.1177/03000605261458669
  29. Pediatr Pulmonol. 2026 Jul;61(7): e71729
       INTRODUCTION: Persons living with cystic fibrosis (PwCF) have experienced fewer exacerbations and symptom burden over the last decade, largely thanks to widespread uptake of highly effective modulator therapy (HEMT). With these advancements, there have been interest in the community regarding adjustments to the care model. However, there is a paucity of data with which to guide discussions for clinical follow-up.
    OBJECTIVE: The goal of the survey is to better understand the components of clinical care that are perceived as important when PwCF and their healthcare providers are considering the timing of routine clinical evaluations.
    METHODS: The survey asked predominantly United States PwCF and healthcare providers via CF Community listservs which factors should be considered when determining the interval between routine clinic visits. These included pulmonary function, respiratory symptoms, use of HEMT, pulmonary exacerbations (PExs), and co-morbidities.
    RESULTS: The survey was completed by 152 PwCF and 177 medical providers. Pediatric providers and PwCF were comfortable with higher baseline lung function in comparison to adult providers when considering visit extensions. PwCF and pediatric providers felt more frequent visits were required in comparison to adult providers. PwCF were more tolerant of prior PExs requiring IV antibiotics. There were no differences between groups with respect to the maximum number of PExs requiring oral antibiotics in the previous year to safely extend the interval between visits.
    CONCLUSION: The survey identified and quantified factors that PwCF, adult providers, and pediatric providers felt were important when considering adjusting the interval between clinic visits.
    Keywords:  Care Model; Cystic Fibrosis; Highly effective modulator therapy
    DOI:  https://doi.org/10.1002/ppul.71729
  30. Expert Rev Anti Infect Ther. 2026 Jul 10. 1-18
       INTRODUCTION: Complicated urinary tract infection (cUTI) is a common and heterogeneous infection associated with substantial morbidity, high healthcare utilization, and increasing antimicrobial resistance. Evolving definitions, increasing device use, and changing patient populations have altered its epidemiology and management. Marked variability in diagnostic criteria, clinical trial endpoints within and outside registrational settings, and treatment strategies complicates clinical decision-making and interpretation of therapeutic advances.
    AREAS COVERED: This review examines contemporary cUTI epidemiology, classification frameworks, and drivers of disease burden. It evaluates resistance trends and their therapeutic implications, alongside stewardship-based management strategies, including empiric antibiotic selection, intravenous-to-oral transition, treatment duration, and source control. Challenges in catheter-associated infection, recurrence, and regulatory endpoint design are discussed, together with the emerging role of novel agents targeting resistant Gram-negative pathogens.
    EXPERT OPINION: Rising multidrug resistance and limited oral options are reshaping cUTI management, necessitating individualized, stewardship-aligned therapy guided by illness severity and local epidemiology. Current regulatory endpoints inadequately reflect patient-centered outcomes, particularly in the context of asymptomatic bacteriuria. Expanding availability of effective oral agents may enable earlier discharge and outpatient care. Integration of rapid diagnostics and risk stratification will be essential to optimize therapy, limit resistance, and improve outcomes.
    Keywords:  Complicated urinary tract infection; ESBL-producing Enterobacterales; antimicrobial resistance; asymptomatic bacteriuria; beta-lactam/beta-lactamase inhibitor; multidrug-resistant Enterobacterales; oral step-down therapy; recurrent urinary tract infection
    DOI:  https://doi.org/10.1080/14787210.2026.2700381
  31. Microb Genom. 2026 Jul;12(7):
      Viruses interact with all domains of life and play fundamental roles in shaping biological systems from individual hosts to global ecosystems. Yet their identification remains difficult due to a lack of a universal marker gene and the extensive diversity of viral genomes. Despite this, the speed of viral discovery is quickly increasing, driven by the growing number of virome studies, improved sequencing technologies and the decreased cost of sequencing. In this review, we examine the evolution of virus identification approaches from classical and molecular methods to contemporary genome-resolved and computational frameworks. By aggregating genome-resolved virome studies from 2010 to early 2026 that meet defined criteria (n=502), we synthesize the current landscape of virus identification methods, including similarity-based, sequence-based artificial intelligence (AI) and hybrid approaches. We also highlight the key limitations of the current methods, particularly biases in reference databases that contribute to persistent viral 'dark matter'. Finally, we identify emerging opportunities for the field in structure-based and AI-driven approaches that extend detection beyond sequence similarity and outline how these integrative frameworks are poised to improve virus discovery across ecosystems.
    Keywords:  metagenomics; phage; viral ecology; virome; virus
    DOI:  https://doi.org/10.1099/mgen.0.001785
  32. J Oral Biol Craniofac Res. 2026 Jul-Aug;16(4):16(4): 101482
       Background: Periodontal diseases represent a complex dysbiosis-driven inflammatory condition, where the transition from health to gingivitis and periodontitis is accompanied by distinct microbial shifts. Emerging evidence highlights the significance of less-studied genera such as Neisseria, Dialister, and Filifactor in shaping periodontal outcomes. This study aimed to investigate the salivary distribution of Neisseria, Dialister, and Filifactor species across periodontal health, gingivitis, periodontitis, and gingival recession using next-generation sequencing (NGS).
    Methods: Whole saliva samples were collected from 40 participants (10 per group) classified according to the American Academy of Periodontology criteria. Microbial DNA was extracted and subjected to 16S rRNA sequencing (V3-V4 region, Illumina MiSeq). Species-level classification was performed using the Human Oral Microbiome Database. Frequency distributions were compared across groups using Fisher's exact test, with significance set at p < 0.05.
    Results: Distinct patterns were observed. Several commensal Neisseria species, including N. subflava (p = 0.001), N. elongata(p = 0.015), and N. polysaccharea (p = 0.001), showed significantly reduced prevalence in periodontitis compared with health and gingivitis. In contrast, Dialister pneumosintes exhibited a sharp increase in all diseased groups (p = 0.002). Filifactor alocis was markedly enriched in gingivitis, recession, and periodontitis (p = 0.011), suggesting its strong association with disease states.
    Conclusion: The findings demonstrate a characteristic microbial shift in saliva: health-associated Neisseria species decline with disease progression, while anaerobic taxa such as D. pneumosintes and F. alocis expand. These results align with the polymicrobial synergy and dysbiosis model and underscore the potential of these species as salivary biomarkers for early detection and monitoring of periodontal disease.
    Keywords:  Dialister; Filifactor; Neisseria; Next-generation sequencing; Periodontal disease; Saliva microbiome
    DOI:  https://doi.org/10.1016/j.jobcr.2026.101482
  33. medRxiv. 2026 Jul 02. pii: 2026.06.30.26356898. [Epub ahead of print]
      Periodontitis, a chronic inflammatory disease affecting approximately 40% of U.S. adults aged 30 years and older, is characterized by dysbiosis of the dental plaque microbiome. However, although scaling and root planing (SRP) is the cornerstone of periodontal treatment, its effects on the taxonomic composition and functional potential of the dental plaque microbiome remain incompletely understood. In this study, we used whole-metagenome shotgun sequencing to characterize taxonomic composition and functional potential in dental plaque microbiomes collected from 39 patients with Stage II or III generalized periodontitis before and 3-4 months after SRP. Consistent with clinical improvement, periodontal therapy significantly reduced bleeding on probing and plaque index. Whole-metagenome shotgun sequencing identified 3.18 million non-redundant genes and 12,353 microbial species across 78 samples, revealing increased gene and species richness after treatment, along with a significant restructuring of microbial community. Established periodontal pathogens, including Porphyromonas gingivalis and Tannerella forsythia, as well as the emerging pathogen Escherichia coli, decreased following treatment, whereas health-associated early colonizers, including multiple Actinomyces species and Streptococcus cristatus, increased. Functional annotation using the Carbohydrate-Active Enzymes (CAZy) database identified treatment-associated differences in several carbohydrate-active enzymes, including multiple glycosyltransferases, indicating remodeling of the predicted functional potential of the dental plaque microbiome. These findings demonstrate that successful SRP promotes coordinated taxonomic and predicted functional remodeling of the dental plaque microbiome and highlight the value of shotgun metagenomic sequencing for characterizing both taxonomic and functional recovery following periodontal therapy.
    Keywords:  dental plaque microbiome; functional profiling; periodontitis; scaling and root planing; shotgun metagenomics
    DOI:  https://doi.org/10.64898/2026.06.30.26356898
  34. Sci Rep. 2026 Jul 09.
      Diabetic foot infections (DFIs) are complex, polymicrobial conditions that delay wound healing, increase the risk of lower limb amputation, and contribute to higher mortality among patients with diabetes mellitus. Traditional culture-based diagnostic methods often fail to identify the full diversity of wound-associated microorganisms, particularly fastidious and anaerobic species. This study aimed to characterize the microbial composition of DFIs through 16S rRNA gene sequencing and to examine its relationship with disease severity and wound healing outcomes. A cross-sectional comparative study was conducted on 300 participants divided into three groups of equal numbers: healthy controls, patients with mild DFIs, and patients with severe DFIs. Superficial and deep wound swabs were collected under aseptic conditions. Bacterial genomic DNA was extracted, and the V3 to V4 region of the 16S rRNA gene was sequenced using the Illumina MiSeq platform. Sequence processing and quality control were performed through the QIIME2 DADA2 pipeline, while taxonomic classification was assigned using the SILVA 138 database. Microbial diversity analyses included Shannon and Simpson indices for alpha diversity, however,  Bray-Curtis and weighted UniFrac metrics for beta diversity. Significant differences in microbial community composition were observed among the study groups (PERMANOVA, p < 0.001), although overall amplicon sequence variant richness showed no significant variation (p = 0.12). Alpha diversity was highest in mild DFIs and declined significantly in severe infections (p < 0.001), indicating progressive microbial dysbiosis with increasing disease severity. Proteobacteria dominated all cohorts (> 98.2%), with Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Delftia acidovorans among the most prevalent taxa. Beta diversity analyses demonstrated partial clustering according to clinical severity, suggesting subtle but biologically meaningful microbial restructuring. Reduced microbial diversity and increased abundance of opportunistic pathogens are associated with poor healing outcomes in DFIs. These findings highlight the clinical relevance of microbiome profiling to enhance understanding of disease progression and optimize therapeutic strategies. Severe DFIs are associated with reduced microbial diversity and enrichment of opportunistic Gram-negative pathogens, particularly within the order Pseudomonadales. These findings highlight the limitations of conventional culture methods and support the integration of microbiome-based diagnostics for improved risk stratification and targeted antimicrobial management in diabetic foot infections.
    Keywords:  16S rRNA sequencing; Diabetic foot infection; Microbial diversity; Microbiome; Wound healing
    DOI:  https://doi.org/10.1038/s41598-026-54045-7
  35. Nat Commun. 2026 Jul 06.
      Chronic wounds represent a major clinical challenge driven by sustained inflammation, proteolytic imbalance, microbial colonisation, and impaired tissue regeneration. This review critically examines 2D and 3D in vitro models used in chronic wound research, evaluating their capacity to recapitulate chronicity across venous leg ulcers, diabetic foot ulcers, and pressure ulcers. Current systems lack the biochemical complexity required to reproduce key features of the non-healing phenotype. Building on quantitative clinical wound exudate data, we propose a feature-driven, aetiology-stratified framework that provides modular design considerations for in vitro models and chronic wound simulating media.
    DOI:  https://doi.org/10.1038/s41467-026-75311-2
  36. Curr Top Microbiol Immunol. 2026 Jul 08.
      Periodontitis is a highly prevalent chronic inflammatory disease characterized by irreversible destruction of the tooth-supporting tissues. Although classically interpreted as the consequence of excessive inflammation that drives microbial dysbiosis, accumulating experimental and clinical evidence indicates that periodontitis can be more precisely described as a disorder of failed inflammatory resolution. In periodontal tissues-constantly exposed to microbial challenge-resolution is not a terminal event but a constitutive biological requirement essential for maintaining tissue homeostasis. This chapter examines the molecular and cellular mechanisms through which pro-resolving pathways become dysregulated in periodontitis, with particular emphasis on imbalances in lipid mediator networks, defective biosynthetic class switching, impaired receptor-mediated signaling, altered leukocyte fate decisions, and disruption of osteoimmune coupling. We further discuss how these resolution defects are functionally expressed across immune, stromal, and bone compartments, and how they reshape the inflammatory microenvironment and host-microbiome interactions. Finally, we evaluate the implications of these mechanisms for resolution pharmacology, highlighting how restoration of endogenous termination and repair programs-rather than suppression of inflammatory initiation-offers a biologically grounded therapeutic paradigm. Collectively, this chapter positions periodontitis as both a disease-specific manifestation of resolution failure and a tractable translational model for advancing resolution-based therapeutic strategies with potential relevance beyond oral tissues.
    Keywords:  Dysbiosis; Immune regulation; Inflammation; Periodontitis; Pro-resolving mediators; Resolution biology; SPMs; Tissue repair
    DOI:  https://doi.org/10.1007/82_2026_347
  37. ACS Biomater Sci Eng. 2026 Jul 10.
      Diabetic wounds (DWs), characterized by pathological features of healing stagnation and limited regeneration, pose significant clinical challenges in chronic wound management and contribute to substantial consumption of healthcare resources. Although current clinical interventions heavily rely on debridement, offloading, and traditional wound dressings, their therapeutic efficacy often falls short of expectations due to limitations in providing only a physical barrier function. Furthermore, the pathogenesis of DWs involves a complex interplay of multiple pathological factors, including peripheral neuropathy, peripheral arterial disease, and foot infections, which further complicates wound management. In recent years, hydrogels have demonstrated significant potential in the biomedical field of DW management due to their biological versatility, tunable physicochemical properties, and excellent hydrophilicity. By loading specific therapeutic agents, hydrogels can achieve on-demand drug release tailored to the unique physiological microenvironment of DWs and optimize the microenvironment across different stages of wound healing. This study systematically evaluates smart hydrogel-based integrated diagnosis and therapy strategies by analyzing pathological characteristics and clinical limitations of DWs (particularly diabetic foot ulcers), aiming to provide references for developing clinically translatable dressing systems and establish theoretical frameworks with practical guidelines for next-generation intelligent dressings incorporating AI-driven data and clinical stability.
    Keywords:  AI-driven design; clinical translation; diabetic foot ulcers; microenvironment remodeling; smart hydrogels; spatiotemporal release; theranostics
    DOI:  https://doi.org/10.1021/acsbiomaterials.6c00731
  38. Transl Pediatr. 2026 Jun 30. 15(6): 243
       Background and Objective: Asthma and allergic diseases are increasingly prevalent chronic inflammatory disorders characterized by immune dysregulation, epithelial barrier impairment, and marked clinical heterogeneity. Increasing evidence suggests that both the gut microbiome and the respiratory microbiome are associated with disease initiation, phenotype expression, and exacerbation risk. This narrative review aims to synthesize current evidence on microbiome alterations associated with asthma and allergic diseases, with particular emphasis on mechanistic pathways, bidirectional gut-lung axis interactions, and microbiome-targeted therapeutic opportunities.
    Methods: We conducted a narrative review of recent English-language literature on the gut microbiome, respiratory microbiome, asthma, allergic diseases, microbial metabolites, and microbiome-based interventions. Relevant studies and reviews were identified through literature screening and were selected for their relevance to early-life microbial colonization, disease-associated dysbiosis, immune regulation, gut-lung axis biology, and translational strategies.
    Key Content and Findings: Current evidence indicates that early-life gut microbial colonization, airway microbial dysbiosis, and altered metabolite production are associated with allergic susceptibility, inflammatory phenotype, exacerbation risk, and disease progression. The strength of evidence differs across domains: human cohort and clinical studies most strongly support associations between early-life microbial patterns, airway dysbiosis, and disease phenotypes, whereas many mechanistic pathways remain supported primarily by preclinical or experimental data. Key mechanisms include mucosal microbiome-immune crosstalk, local airway epithelial-microbial interactions, short-chain fatty acid-mediated immune regulation, tryptophan and bile acid signaling, epithelial barrier dysfunction, viral-microbiome interactions, and epigenetic modulation. The gut-lung axis provides a bidirectional framework linking intestinal and airway microbial ecosystems through immune, metabolic, inflammatory, infectious, and treatment-related pathways. Emerging interventions show different levels of evidence and should not be interpreted as equally mature therapeutic strategies.
    Conclusions: The gut and respiratory microbiomes are important components of the pathogenic network underlying asthma and allergic diseases and may represent future targets for prevention and therapy. However, many reported microbial signatures remain associative, and stronger standardization, longitudinal validation, functional studies, and evidence-stratified clinical trials are needed before microbiome-informed precision medicine can be broadly implemented in routine care.
    Keywords:  Asthma; allergic diseases; gut microbiome; gut-lung axis; respiratory microbiome
    DOI:  https://doi.org/10.21037/tp-2026-0360
  39. Curr Protoc. 2026 Jul;6(7): e70405
      Viral metagenomics is an increasingly powerful tool for understanding the function and structure of viruses across the diverse environments of our planet. However, decoding the functional potential of prokaryotic viral metagenomes is extremely challenging. Pharokka, Phold, and Phynteny are complementary open-source prokaryotic viral genome annotation tools that utilize a variety of bioinformatics approaches to maximally annotate viral metagenomes. This article describes a protocol for installing and running these tools on a viral metagenomic dataset, followed by visualization of annotations using our client-side Phold Plot web assembly application. © 2026 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Prokaryotic viral metagenome annotation with Pharokka Basic Protocol 2: Enhanced prokaryotic viral metagenome protein annotation using protein structures with Phold Basic Protocol 3: Further prokaryotic viral metagenome protein annotation using genome synteny and protein language models with Phynteny Basic Protocol 4: Visualization of prokaryotic viral metagenome annotations with Phold Plot web assembly application.
    Keywords:  bacteriophage; genome annotation; metagenomes; prokaryotic viruses; protein function; protein structure
    DOI:  https://doi.org/10.1002/cpz1.70405
  40. Microbiol Spectr. 2026 Jul 06. e0036726
      Long-term associations within an individual host allow bacterial populations to diversify over time, sometimes resulting in the coexistence of multiple species or variants of the same species. Traditional methods for identifying infective agents generally involve isolating a single pathogen and potentially even a single colony from a given sample. While screening samples for virulent or difficult-to-treat pathogens is an important part of informing clinical treatment and correlative research, these reductive methods alone do not provide researchers or healthcare providers with the potentially important perspective on the true pathogen population. In this study, we begin to address this limitation by comparing the phenotypic and genotypic diversity of single colonies and pooled isolates of Staphylococcus aureus taken from fresh sputum samples from three patients with cystic fibrosis. Additionally, we compare the results collected in our research laboratory to those processed by the Emory Clinical Microbiology Laboratory with the identical sputum samples. We identified unrelated coexisting lineages in two out of three sputum samples, as well as clinically relevant population structures that were not apparent from studying single-colony isolates alone. Altogether, our observations presented here demonstrate that the true nature and phenotype of a clinically isolated pathogen can be missed with standard sampling methods when assessing chronic infections. More broadly, this work outlines the potential impact that comprehensive population-level sampling may have for both research efforts and more effective treatment practices.
    IMPORTANCE: When obtaining bacterial isolates from infections, it is important to consider the ecological biases introduced by methods used for collection and processing. In this study, we demonstrate how reductive sampling and processing methods traditionally used by clinical microbiology labs often do not adequately capture complex and clinically relevant traits present in diverse pathogen populations. When treating or studying bacteria like Staphylococcus aureus that can maintain multiple variants within a population over a long period of time, it may be more effective and informative to employ sampling methods that account for the potential diversity within a population, as outlined in our approach presented here.
    Keywords:  Staphylococcus aureus; cystic fibrosis; intraspecific diversity; microbial ecology and evolution
    DOI:  https://doi.org/10.1128/spectrum.00367-26
  41. J Nanobiotechnology. 2026 Jul 09.
      The effective treatment of bacterial infections requires rapid and selective enrichment of antibacterial agents on bacterial surfaces within infectious microenvironments. Transition metal ion-based antibacterial agents show broad-spectrum bactericidal activity, but they usually rely on passive diffusion and stochastic bacterial contact, limiting their ability to establish sufficient local doses within short treatment windows. Herein, an M13 phage-mediated targeting strategy was developed for the rapid enrichment and delivery of copper ion-protocatechuic acid nanoparticles (CP NPs). Through phage display, an M13 phage targeting methicillin-resistant Staphylococcus aureus (MRSA-targeting phage, MTP) and an M13 phage targeting Pseudomonas aeruginosa (P. aeruginosa-targeting phage, PTP) were identified. MTP and PTP retained the typical filamentous morphology of M13 phage and selectively adhered to corresponding bacteria within 1 min. Protocatechuic acid (PCA) was then used as a polyphenolic bridge for phage-surface adhesion and Cu2+ coordination, yielding CP@MTP and CP@PTP, which integrate bacterial recognition, metal-polyphenol assembly, and copper-based antibacterial activity into filamentous delivery scaffolds. After only 10 min of bacterial exposure, CP@MTP selectively reduced MRSA by 3 log, while CP@PTP reduced P. aeruginosa by 1.7 log, likely owing to rapid phage-mediated CP NP enrichment on bacterial surfaces. Transcriptomic analysis further revealed bacterial stress responses induced by targeted copper delivery. In zebrafish larval tail-fin infection models, CP@MTP and CP@PTP effectively eradicated corresponding bacteria and reduced neutrophil recruitment. In a murine P. aeruginosa pneumonia model, CP@PTP prolonged lung retention, reduced pulmonary bacterial burden, and alleviated inflammatory lung injury. This study establishes targeted M13 phages as spatial regulators for rapid and precision antibacterial therapy.
    Keywords:  Antibacterial therapy; Metal-phenolic nanoparticles; Phage display; Targeted delivery
    DOI:  https://doi.org/10.1186/s12951-026-04803-6
  42. Sci Transl Med. 2026 Jul 08. 18(857): eadz4589
      Adherent-invasive Escherichia coli (AIEC) exhibits proinflammatory properties and has been implicated in the pathogenesis of Crohn's disease (CD), a form of inflammatory bowel disease (IBD). Antibiotic use in CD lacks specificity and may worsen microbiome disruption, prompting interest in bacteriophages (phages) for targeted microbiome editing. Here, we identified HER259, a phage active against clinical AIEC isolates. HER259 ameliorated colitis in gnotobiotic models and attenuated the virulence of AIEC strain NRG857c, including suppression of the FimH adhesin through inversion of the fimS promoter to its "off" orientation. The effects were confirmed in CD-microbiota colitis models. Withdrawal of HER259 treatment led to reversion of the fimS promoter and reactivated colitis. The HER259 phage also enhanced the therapeutic effect of subtherapeutic budesonide independent of microbial drug metabolism. These findings support targeted phage therapy as an adjunct treatment approach in IBD, demonstrating modulation of bacterial virulence and improved response to conventional treatments that may reduce drug-related side effects.
    DOI:  https://doi.org/10.1126/scitranslmed.adz4589
  43. SLAS Technol. 2026 Jul 07. pii: S2472-6303(26)00066-X. [Epub ahead of print]40 100452
      Crohn's disease is a long-term inflammatory disorder arising from the interaction of genetic risk factors, immune system dysfunction, and alterations in gut microbiota. Variability in clinical phenotypes and lack of biomarker specificity hinder the efficiency of current traditional diagnostic and treatment approaches. This review aims to assess how AI- and ML-driven multi-omics offer comprehensive insights into pathogenicity, thereby enhancing diagnostic techniques and personalized therapeutic approaches in CD. Current studies employ integration of multi-omics like genomics, proteomics, transcriptomics, metabolomics, and microbiome analysis in CD with AI and ML for significant advancement of biomarker discovery and clinical applications. Emerging evidence reveals that CD is a multi-factorial disorder involving host genetics, immune dysfunction, and microbiome shifts. Integration of advanced AI/ML models with multi-omics data can predict disease-specific biomarkers for easy diagnosis and facilitate precision medicine to enhance therapies. For a successful clinical implementation of an AI/ML model with multi-omics in CD, a standardized data framework and large-scale validation are needed. Additionally, future research should focus on developing interpretable AI models, real-time monitoring systems, and theranostic platforms to enhance precision healthcare delivery.
    Keywords:  Artificial intelligence; Crohn’s disease; Immunity; Machine learning; Microbiota; Multi‑omics; Precision medicine
    DOI:  https://doi.org/10.1016/j.slast.2026.100452
  44. JMIR Diabetes. 2026 Jul 08. 11 e77925
       Background: Diabetic foot ulcers (DFU) are serious complications of diabetes that contribute substantially to morbidity, mortality, and health care burden. Accurate and timely wound assessment is essential for effective DFU management; however, conventional assessment methods are limited by subjectivity, time constraints, and interobserver variability.
    Objective: This scoping review aimed to map and synthesize evidence regarding the development and application of artificial intelligence (AI)-based models for DFU assessment.
    Methods: A scoping review was conducted following the Arksey and O'Malley framework and reported according to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines. Literature searches were performed in PubMed, ProQuest, and Scopus for studies published between 2014 and 2026. Study selection and data charting were conducted independently by two reviewers using predefined inclusion criteria based on the PCC (population, concept, context) framework. Extracted data were synthesized narratively and categorized according to major AI application domains.
    Results: A total of 654 records were identified, of which 46 studies met the inclusion criteria. The included studies predominantly focused on image segmentation, diagnostic classification, and risk prediction or monitoring of DFUs. Convolutional neural networks were the most commonly applied models, with performance evaluated using metrics such as accuracy, Dice similarity coefficient, and area under the curve. Most studies relied on retrospective, single-center datasets, with limited external validation and minimal real-world clinical implementation.
    Conclusions: AI-based models demonstrate strong potential to enhance DFU assessment and monitoring by improving accuracy and efficiency. However, significant gaps remain in terms of dataset diversity, external validation, and integration into clinical workflows. Future research should prioritize prospective validation, standardized datasets, and real-world implementation to support safe and effective clinical adoption.
    Keywords:  artificial intelligence; deep learning; diabetic foot ulcers; diabetic wound; scoping review
    DOI:  https://doi.org/10.2196/77925
  45. Front Dent Med. 2026 ;7 1873996
       Aim: This study evaluated the diagnostic potential of salivary total matrix metalloproteinase-8 (tMMP-8), adiponectin, and resistin in prediabetic adults with and without periodontitis and examined their associations with systemic and periodontal parameters.
    Materials and methods: Systemically healthy and prediabetic adults, categorized by periodontal status, underwent clinical, anthropometric, and metabolic assessments. A total of 84 adults aged 25-55 years were enrolled and stratified into four groups: prediabetes with periodontitis (PreDM-PD, n = 24), prediabetes with periodontal health (PreDM-PH, n = 19), systemically healthy with periodontitis (SH-PD, n = 22), and systemically and periodontally healthy controls (SH-PH, n = 19). Unstimulated saliva was collected to quantify tMMP-8, adiponectin, and resistin by sandwich ELISA. Statistical analyses included group comparisons (one-way ANOVA with Bonferroni post-hoc correction; Kruskal-Wallis with Dunn's test for non-normally distributed variables), correlation analysis of biomarkers with systemic and periodontal measures, and principal component analysis (PCA) to define a composite inflammatory profile.
    Results: Participants with periodontitis had significantly higher periodontal parameters (p < 0.001). Salivary tMMP-8 was elevated in prediabetic individuals with periodontitis compared to other groups (p < 0.001), whereas adiponectin was lower in prediabetic groups versus controls (p < 0.01). tMMP-8 correlated positively with BMI, HbA1c, probing pocket depth (PPD), and clinical attachment loss (CAL). Adiponectin inversely correlated with HbA1c, PPD, CAL, and bleeding on probing. Resistin showed a weak positive correlation with CAL. PCA revealed an inflammatory profile (high tMMP-8, low adiponectin) explaining 37.1% of variance (KMO = 0.58; Bartlett's χ² = 22.86, p < 0.001), effectively distinguishing prediabetic with periodontitis from healthy controls (AUC = 0.925, p < 0.001; sensitivity 87.5%, specificity 89.5%, Youden J = 0.77) and showing acceptable accuracy in periodontal health. Between-group differences for tMMP-8, adiponectin, PPD, CAL and BoP remained statistically significant after adjustment for age (ANCOVA, all p < 0.01).
    Conclusion: Salivary tMMP-8 and adiponectin composite profiles outperform single markers, supporting their use in non-invasive periodontal risk screening in metabolically vulnerable adults. Elevated tMMP-8 links periodontal and metabolic inflammation in prediabetes.
    Keywords:  adipokines; adiponectin; enzyme-linked immunosorbent assay (ELISA); periodontitis; prediabetes; resistin; salivary matrix metalloproteinases (MMP-8)
    DOI:  https://doi.org/10.3389/fdmed.2026.1873996
  46. Diagn Microbiol Infect Dis. 2026 Jul 02. pii: S0732-8893(26)00290-7. [Epub ahead of print]116(3): 117540
      Periodontal diseases are polymicrobial infections driven by complex interactions between anaerobic pathogens and host immune responses within the periodontal pocket. Accurate detection and characterization of these pathogens are critical for early diagnosis, disease risk assessment, and effective therapeutic intervention. This review aims to critically evaluate conventional anaerobic culture and advanced molecular diagnostic techniques for the detection and characterization of periodontal pathogens, highlighting their respective advantages, limitations, and clinical relevance. A comprehensive analysis of existing literature was conducted focusing on traditional culture-based approaches and emerging molecular technologies, including polymerase chain reaction (PCR), quantitative PCR (qPCR), 16S rRNA gene sequencing, next-generation sequencing (NGS), and multi-omics strategies such as metagenomics, metatranscriptomics, proteomics, and metabolomics. Anaerobic culture remains the gold standard for microbial isolation, enabling phenotypic characterization, antimicrobial susceptibility testing, and functional studies. However, it is labor-intensive, time-consuming, and limited in detecting fastidious, slow-growing, or viable-but-non-culturable microorganisms. In contrast, molecular techniques offer rapid, sensitive, and comprehensive detection of key periodontal pathogens, including Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola. Advanced omics approaches further provide insights into microbial functionality, virulence, and host-microbe interactions. Nevertheless, molecular methods are limited in assessing microbial viability and antimicrobial susceptibility. The integration of culture-based and molecular diagnostic approaches enhances diagnostic accuracy and supports early, targeted therapeutic interventions. This combined strategy facilitates personalized treatment planning, improves clinical outcomes, and helps reduce inappropriate antimicrobial use in periodontal therapy. Both anaerobic culture and molecular diagnostics possess distinct yet complementary strengths. An integrated diagnostic approach combining phenotypic and high-resolution molecular techniques is essential for improving diagnostic accuracy, enabling personalized treatment strategies, advancing precision periodontal care, and contributing to Good Health and Well-Being through improved oral health outcomes and responsible antimicrobial stewardship.
    Keywords:  Anaerobic culture; Good Health and Well-Being; Molecular diagnostics; Oral biofilms; Periodontal microbiology; Periodontal pathogens; Responsible Consumption and Production
    DOI:  https://doi.org/10.1016/j.diagmicrobio.2026.117540
  47. World J Biol Psychiatry. 2026 Jul 09. 1-15
       BACKGROUND/OBJECTIVES: Depression and anxiety are increasingly linked to systemic inflammation and microbiome alterations, yet the role of the oral microbiome remains poorly characterised. This systematic review synthesises recent human evidence examining associations between depression or anxiety and (1) peripheral or salivary inflammatory biomarkers and (2) oral microbiome alterations.
    MATERIALS AND METHODS: Following PRISMA 2020 guidance, PubMed, Web of Science, and PsycINFO were searched for studies published between 2016 and 2026. Eligible studies assessed depression, depressive symptoms, anxiety, generalised anxiety disorder (GAD), or PTSD-related symptoms alongside inflammatory biomarkers in blood or saliva and/or oral microbiome profiles. Reference lists of key eligible studies were also screened. Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) or an adapted NOS framework.
    RESULTS: Fifty-three primary studies met eligibility criteria, including 42 studies evaluating inflammatory or salivary biomarkers and 11 studies examining oral microbiome profiles. Depression was associated with alterations in pro-inflammatory markers, particularly CRP, IL-6-related signalling, TNF-α, and other cytokine or chemokine markers. Anxiety-related findings were more heterogeneous. Oral microbiome studies reported altered community composition and taxa associated with depression, anxiety, and trauma-related symptoms, but findings varied by population, sampling site, and adjustment for oral-health and behavioural confounders.
    CONCLUSIONS: Current evidence suggests depression and anxiety-related conditions are associated with low-grade inflammatory activity and alterations in the oral microbiome. These findings support an oral-immune-brain framework for future research, but the current evidence remains largely observational.
    Keywords:  Oral microbiome; anxiety disorders; depression; inflammatory biomarkers; psychoneuroimmunology
    DOI:  https://doi.org/10.1080/15622975.2026.2688864
  48. BMC Microbiol. 2026 Jul 09.
       BACKGROUND: Intensive care unit environments are a critical reservoir of antimicrobial-resistant bacterial species and facilitate the transmission of nosocomial infections. This unit harbors multidrug-resistant organisms, thereby complicating the management of infectious diseases within clinical settings, particularly in resource-limited countries. This study, therefore, aimed to determine the occurrence and antimicrobial resistance profiles of bacteria, including Extended-spectrum beta-lactamase- and Carbapenemase-producing isolates, in the intensive care units of two hospitals in Addis Ababa, Ethiopia.
    METHODS: A repeated cross-sectional study was conducted in Addis Ababa, Ethiopia, from July 2024 to April 2025. A total of 239 swab samples were collected from adult and neonatal intensive care unit environments during both the dry and rainy seasons. Samples were collected and processed aseptically. Bacterial identification and antimicrobial susceptibility testing were performed according to CLSI guidelines.
    RESULTS: From the total samples collected, 162/239 (67.8%) bacterial isolates were recovered from the Intensive Care Unit environment. Klebsiella pneumoniae 22/162 (13.6%) and Pseudomonas aeruginosa 21/162 (13%) were the most frequently isolated bacterial species. All P. aeruginosa were resistant to ceftazidime, while 19/22 (86.3%) and 18/22 (81.8%) of K. pneumoniae were resistant to cefuroxime and cefotaxime, respectively. All S.haemolyticus were also resistant to penicillin, and 8/12 (66.7%) of Enterococcus spp were resistant to erythromycin. Multidrug-resistant bacteria were seen in 89/150 (59.3%) of isolates. The highest multidrug resistance rate was obtained for Pseudomonas aeruginosa 18/21 (85.7%), followed by Klebsiella pneumoniae 16/22 (72.7%) and Acinetobacter spp 8/11 (72.7%). Extended-spectrum β-lactamase-producing isolates accounted for 23/105 (21.9%), and Carbapenemase-producers comprised 10/105 (9.5%).
    CONCLUSION: The environments within intensive care units are conducive to the proliferation of multidrug-resistant microorganisms, encompassing bacterial isolates that produce extended-spectrum beta-lactamases and carbapenemases, thereby complicating the management of infectious diseases. Consequently, it is crucial to address the issue of antimicrobial resistance in this critical setting to mitigate the incidence and dissemination of resistant bacteria, which may lead to the emergence of nosocomial infections.
    Keywords:  Antimicrobial resistance; Carbapenemase; Infection control; Intensive care Unit
    DOI:  https://doi.org/10.1186/s12866-026-05361-5
  49. J Telemed Telecare. 2026 Jul 06. 1357633X261462025
      IntroductionChronic wounds which do not heal as expected, are common in residential aged care homes (RACHs). While specialised wound care is essential for improving outcomes, access is challenging in RACHs. Emerging virtual interventions are known to improve access to wound care, but little is known about use in this setting. This scoping review identifies and maps virtual wound care use in RACHs.MethodsAn electronic search of Medline, CINAHL, Embase, AgeLine, IEEE Xplore, ACM digital library and clinical trial registries was conducted from database inception to March 2026. Studies were screened and data extracted by two independent reviewers using a reviewer-developed tool.ResultsOf the 17 included studies, a combined model of telehealth and store and forward was most frequently used (n = 9). Virtual wound care was used for both diagnosis and management (n = 15) and commonly delivered by teams of clinicians (n = 8). Included studies demonstrated wound care could be delivered safely and facilitated clinical decision-making. Acceptability of virtual wound care by residents, families, staff and other care providers was high. Reliable internet, stable workforce and adjunct in-person care were enablers to virtual interventions. Lack of training participation, workforce shortages and technology limitations were perceived barriers to virtual wound care.ConclusionsCurrent evidence indicates that virtual wound care is being used in RACHs though it remains under investigated. Addressing workforce, training, and technology barriers can support broader implementation of virtual wound care and improve chronic wound outcomes for aged care residents.Review registrationOpen Science Framework https://osf.io/j97bt.
    Keywords:  Chronic wound care; nursing homes; residential aged care; teledermatology; telehealth; virtual care
    DOI:  https://doi.org/10.1177/1357633X261462025
  50. Adv Sci (Weinh). 2026 Jul 08. e23904
      Biofilms, a major cause of chronic bacterial infections, present significant treatment challenges due to their protective extracellular matrix that shields bacteria from both antibiotics and host immune defenses. To treat biofilms more effectively, here we discovered a biofilm-binding peptide from a phage library and verified that it selectively bound the polysaccharides on the biofilm. We then engineered M13 phage into trifunctional nanofibers displaying the biofilm-binding peptide at the tip and carrying gold nanoparticles (AuNPs, as photothermal agents) and tetrakis(4-carboxyphenyl) porphyrin (TCPP, as a photosensitizer) on the sidewall for combined phototherapy. This design enhances binding/anchoring and eradication of biofilms by leveraging the unique properties of each component. The phage nanofibers efficiently bound biofilms and promoted the transfer of heat and penetration of reactive oxygen species (ROS) into the biofilm, leading to cell death. Therefore, under light irradiation, the engineered phage nanofibers effectively eradicated the biofilms by AuNP-induced photothermal therapy (PTT) and TCPP-assisted photodynamic therapy (PDT) in a biofilm-associated skin wound model. Transcriptomic profiling suggests stress-response signatures consistent with oxidative/thermal injury. This study presents a promising ternary synergistic strategy for eradicating biofilms, potentially improving clinical outcomes in wound infection management.
    Keywords:  M13 phage; biofilm; photodynamic therapy; photothermal therapy
    DOI:  https://doi.org/10.1002/advs.202523904
  51. BMC Microbiol. 2026 Jul 04.
       BACKGROUND: The increase in cases of infectious diseases related to multidrug-resistant bacteria and the spread of multidrug-resistant genes have driven the search for therapeutic alternatives that can circumvent this global phenomenon. One of these alternatives is the use of bacteriophages, which are viruses capable of infecting and killing specific bacteria. Klebsiella pneumoniae species complex (KpSC) is an important opportunistic group associated with multidrug resistance. This group includes Klebsiella quasipneumoniae subsp. similipneumoniae, a species recognized as a clinically relevant pathogen, and that was used as a host (designated Klebsiella KH1) to isolate the phage characterized in the present study. The characterization of new phages is essential to expand the therapeutic arsenal and to improve our understanding on phage diversity. In this study, we evaluated a Klebsiella bacteriophage named KP47 that was isolated from sewage in the United Kingdom. We performed phage biological and genomic characterization in order to assess its therapeutic attributes. KP47 represents a newly isolated Klebsiella phage, being able to infect both K. pneumoniae and K. quasipneumoniae subsp. similipneumoniae, which also shows evidence of depolymerase activity and an efficient bacteriolytic performance.
    RESULTS: The phage KP47 showed a typical morphology of the Caudoviricetes class, with a capsid of 48 nm and a tail of 161 nm. Its genome has 47,396 bp, 63 CDSs, and a GC content of 57.52%, which apparently encodes a depolymerase. ViPTree analysis placed KP47 near Drexlerviridae-related phages, while comparative analyses using representative RefSeq genomes revealed low intergenomic similarity. This phage demonstrated strictly lytic behavior and fast adsorption (90% in 6 min). MOI experiments indicated complete inhibition of bacterial growth in MOIs ≥ 1. The phage infected two out of nine tested strains belonging to the strains of KpSC.
    CONCLUSIONS: In this study, we described the Klebsiella phage KP47, likely representing a new viral genus, that exhibits a strictly lytic lifestyle, rapid adsorption (90% within 6 min), and an effective bacterial growth inhibition at MOIs ≥ 1. KP47 was able to infect clinically relevant members of the Klebsiella pneumoniae species complex. Further investigations of its potential to act on biofilms and against Klebsiella species in in vivo models are of interest to evaluate its potential for clinical application.
    Keywords:   Klebsiella pneumoniae species complex; Caudoviricetes; Depolymerase; Phage taxonomy
    DOI:  https://doi.org/10.1186/s12866-026-05359-z
  52. Int J Biol Macromol. 2026 Jul 09. pii: S0141-8130(26)03393-3. [Epub ahead of print] 153448
      Infected wounds remain a critical clinical challenge, predominantly driven by Staphylococcus aureus (S. aureus, especially methicillin-resistant S. aureus, MRSA) biofilm formation, which triggers a vicious cycle of persistent infection, sustained inflammation, and progressive oxidative stress. Current clinical interventions fail to achieve simultaneous bacterial eradication, modulation of inflammation, and tissue regeneration, often with biocompatibility risks, whereas natural polysaccharide-based biomaterials offer a promising engineering strategy to address this dilemma. Herein, based on the nano-cocktail synthesis concept, we developed a caffeic acid (CA)-loaded nanocomposite (CA@ZSH) via green self-assembly from natural carbohydrate polymers (sodium alginate, SA; hyaluronic acid, HA) and zein for comprehensive infected wound therapy. CA was encapsulated in a homogeneous inner matrix of zein and bioactive polysaccharide HA, enabling stable drug loading/sustained release, along with HA-mediated regulation of inflammation and pro-regeneration. This core nanocomplex was further coated with polysaccharide SA as a hydrophilic shell to enhance colloidal stability and maintain a moist wound-healing microenvironment. CA@ZSH exhibited potent anti-S. aureus/MRSA activity via biofilm disruption, plus excellent free radical-scavenging, anti-inflammatory properties, and biocompatibility. In vivo, it markedly accelerated wound healing by upregulating CD31 and VEGF, thereby promoting wound closure, collagen deposition, and angiogenesis. This study provides a facile and robust polysaccharide-based nanotherapeutic engineering strategy for the management of wounds infected with drug-resistant bacteria.
    Keywords:  Biofilm disruption; Caffeic acid; Hyaluronic acid; Sodium alginate; Wound healing
    DOI:  https://doi.org/10.1016/j.ijbiomac.2026.153448
  53. Front Cell Infect Microbiol. 2026 ;16 1864541
       Introduction: This study aims to characterize the dynamic progression of the subgingival microbiome across different stages of periodontitis and to explore its association with levels of systemic chronic inflammation.
    Methods: A total of 148 subjects were enrolled based on predefined inclusion and exclusion criteria. Participants were classified into five groups according to diagnostic criteria: Stage I (n = 25), Stage II (n = 30), Stage III (n = 31), Stage IV (n = 30), and a healthy control group (n = 32). Subgingival samples were collected from all participants and subjected to the 16S rRNA gene sequencing. Peripheral venous blood was obtained to determine blood cell counts and to calculate systemic inflammatory markers. The Spearman's correlation analysis was performed to evaluate associations between subgingival microbial communities and systemic inflammatory markers.
    Results: Patients with Stage IV periodontitis exhibited significantly higher levels of WBC, NEUT, NLR, and SII compared to those with Stage I disease. Notably, NLR and SII were markedly elevated (P < 0.01), while WBC and NEUT also showed statistically significant increases (P < 0.05). Further analysis revealed a positive correlation between the abundance of multiple periodontitis-associated bacterial genera and systemic inflammatory markers.
    Discussion: This study demonstrates that the progression of periodontitis is associated with distinct changes in the subgingival microbial community, and that this microbial dysbiosis is positively correlated with elevated levels of systemic chronic inflammation.
    Keywords:  16S rRNA gene sequencing; microbial succession; periodontitis; subgingival microbiome; systemic inflammation
    DOI:  https://doi.org/10.3389/fcimb.2026.1864541
  54. Phytomedicine. 2026 Jun 29. pii: S0944-7113(26)00743-9. [Epub ahead of print]159 158512
       BACKGROUND: From the discovery of the first antimicrobial drug to nowadays, the development of antimicrobial resistance (AMR) - a silent pandemic among pathogenic microbes has posed a significant challenge to modern healthcare system, necessitating the exploration of novel molecules with potent antimicrobial property.
    OBJECTIVE & METHOD: This review seeks to deliver a thorough analysis of the diverse categories of plant-derived antimicrobials, including their extraction, biosynthesis, purification processes, antimicrobial mechanisms, formulation strategies, and preclinical translation. Rigorous literature search screening was carried out using Google Scholar, Web of Science, PubMed, and Scopus.
    RESULTS: This review represents the first instance of merging artificial intelligence (AI) in advancing phytochemistry research on AMR. Conventional drug development is frequently marked by delayed timeframes, substantial expenses, and complicated issues of target selection, therapeutic efficacy, and safety assessment. Machine learning (ML), deep learning (DL), and natural language processing (NLP), predictive modeling and AI-driven algorithms like BioGPT, DOCK6, SwissADME, DeepTox, etc., facilitate effective drug target selection and toxicity prediction.
    CONCLUSION: Plant-derived secondary metabolites (PSMs) are investigated as a future alternative to traditional medications and are found in stems, leaves, fruits, roots, flowers and seeds of multifaceted plants and proves to be highly effective against various bacterial and fungal pathogen and interferes with the process of quorum sensing and biofilm formation, damages cell membranes and cell wall, enzymes, and induces oxidative stress. Therefore, the review examines contemporary phytochemistry research relevant to the potential development of plant-derived compounds as novel antimicrobial agents.
    Keywords:  Antibacterial; Antifungal; Antimicrobial; Artificial intelligence; Bioactive; Phytochemistry
    DOI:  https://doi.org/10.1016/j.phymed.2026.158512
  55. Front Microbiol. 2026 ;17 1842688
      Antimicrobial resistance (AMR) represents one of the most critical global public health challenges. This review provides a comprehensive overview of the molecular foundation of AMR in human bacterial pathogens, including the biology of resistance genes and the importance of the mobile genetic elements-plasmids, transposons, and integrons-in facilitating the rapid horizontal transfer of resistance determinates across the populations. We critically evaluate current and emerging molecular diagnostic platforms - including targeted polymerase chain reaction (PCR), whole-genome sequencing (WGS), clustered regularly interspaced short palindromic repeats (CRISPR)-based technologies, and metagenomics - emphasizing their comparative performance, limitations, and suitability for point-of-care deployment. The review addresses the translational integration of molecular diagnostics into antimicrobial stewardship programmes and real-time AMR surveillance, with particular attention to the persistent gap between laboratory-generated genomic data and actionable clinical decision-making. Emerging evidence suggests that artificial intelligence (AI) and machine learning hold considerable promise for improving resistance phenotype prediction from genomic data and informing personalized antibiotic therapy, although widespread clinical implementation remains in its early stages. The transition from phenotypic to genotypic strategies represents a significant paradigm shift in AMR, with the potential to substantially improve surveillance, diagnostic accuracy, and therapeutic outcomes, provided that outstanding barriers in infrastructure, standardization, and equity are addressed.
    Keywords:  AMR surveillance; antimicrobial resistance; mobile genetic elements; molecular diagnostics; whole genome sequencing
    DOI:  https://doi.org/10.3389/fmicb.2026.1842688
  56. Dent Mater. 2026 Jul 08. pii: S0109-5641(26)00374-X. [Epub ahead of print]
      Biofilm-associated oral infections, including dental caries, periodontitis, and peri-implantitis, remain fundamentally challenging to manage due to the highly dynamic oral microenvironment and the intrinsic tolerance of multispecies biofilms to conventional antimicrobial strategies. In this context, stimuli-responsive metal-organic frameworks (MOFs) have emerged not merely as drug carriers, but as programmable platforms capable of integrating environmental sensing, on-demand activation, and multimodal antibacterial action. This review critically re-examines smart MOF-based antibacterial systems through the lens of the oral microenvironment, highlighting how pH fluctuations, enzymatic activity, inflammatory redox stress, and biomechanical forces collectively govern MOF stability, activation, and therapeutic performance. We establish oral-specific design principles for stimuli-responsive MOFs, systematically analyze representative MOF families-including ZIFs, Zr-based frameworks, porphyrinic MOFs, and MIL-series materials-and delineate key activation mechanisms driven by pH, enzymes, redox cues, and light. Particular emphasis is placed on the integration of photodynamic therapy (PDT) with controlled antibiotic release, where MOFs enable spatially confined, synergistic disruption of biofilms while mitigating off-target toxicity and antimicrobial resistance. Beyond mechanistic insights, we critically evaluate preclinical evidence across in vitro, ex vivo, and animal models, and identify translational bottlenecks related to biosafety, ion release control, material reproducibility, and clinical deployment in the oral cavity. By bridging oral pathophysiology with materials engineering, this review provides a conceptual and practical framework for the rational design of next-generation, adaptive MOF systems, and offers guidance for prioritizing research directions with the greatest potential for clinical impact in precision antibacterial dentistry.
    Keywords:  Antibacterial dental materials; Metal–organic frameworks (MOFs); Oral biofilm control; Photodynamic therapy (PDT); Stimuli-responsive drug delivery
    DOI:  https://doi.org/10.1016/j.dental.2026.07.001
  57. Syst Rev. 2026 Jul 09.
       BACKGROUND: Living systematic reviews (LSRs) have been published with increasing frequency since the start of the COVID-19 pandemic, but there has been little formal evaluation of their methodological consistency and compliance with best-practice standards. The objective of this overview was to evaluate the extent and nature of current LSRs in health research, as well as the degree to which they acknowledge and adhere to existing methodological standards.
    METHODS: We searched MEDLINE, Embase, Cochrane Database of Systematic Reviews, PROSPERO, Scopus, Epistemonikos, and TRIPdatabase from inception to 24 June 2022. We ran a restricted update search for LSRs published 1 January 2025 to 9 January 2026 to see if conclusions would be similar. We extracted data in duplicate. The primary outcome was the number and proportion of LSRs that conform to existing living standards: criteria and guidance for their need and conduct as published by Cochrane. Secondary outcomes assessed reliability and other reporting aspects. Outcomes were assessed according to explicit author reporting for each review.
    RESULTS: Final analysis included all 23 Cochrane LSRs at the time and a randomly selected 23 non-Cochrane LSRs (among a total of 113). Ten (43%) Cochrane LSRs clearly met the three need criteria for living mode. None of the non-Cochrane LSRs met all three criteria. Cochrane LSRs were also more likely than non-Cochrane LSRs to adhere to Cochrane methodological guidance for the conduct of LSRs, with six (26%) of 23 Cochrane reviews meeting all guidance items. None of the non-Cochrane reviews met all guidance items. In the restricted update (10 LSRs included: five Cochrane and five non-Cochrane), Cochrane LSRs were still more likely to adhere to the three need criteria (four of five, 80%) and five methodological guidance items (three of five, 60%) compared to non-Cochrane LSRs (one of five, or 20% for criteria and guidance adherence). Ten (22%) of all 46 included LSRs were cited by clinical practice guidelines, according to PubMed.
    CONCLUSIONS: This overview highlights a lack of methodological consistency among LSRs, potentially stemming from a lack of awareness of Cochrane's LSR standards. One criterion to become living is that the topic is a priority for decision-making; however, there is little evidence that LSRs are cited frequently in clinical practice guidelines. Establishing clear, objective LSR standards would help to support both Cochrane and non-Cochrane authors and improve evidence-based health care.
    SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022332327.
    Keywords:  Evidence syntheses; Living; Living evidence synthesis; Living systematic review; Review literature; Systematic reviews; Updating systematic reviews
    DOI:  https://doi.org/10.1186/s13643-026-03209-7
  58. Sci Rep. 2026 Jul 04.
      Diabetic foot ulcers (DFUs) are a leading cause of morbidity in patients with diabetes mellitus and a major driver of multidrug-resistant (MDR) bacterial infection in low- and middle-income countries. This cross-sectional study characterised the clinical profile, microbial spectrum and phenotypic/genotypic resistance patterns of DFU-associated bacteria in 224 patients recruited from six tertiary hospitals in Islamabad, Pakistan, between November 2023 and December 2024. Wound swabs, pus aspirates and deep tissue biopsies were collected aseptically and processed on selective and non-selective media; isolates were identified by colony morphology, Gram staining and standard biochemical tests with ATCC reference strains as controls. Antimicrobial susceptibility was determined by Kirby-Bauer disc diffusion against 15 antibiotics following CLSI M100 (2023) guidelines. Plasmid DNA was extracted from all phenotypically β-lactam- or aminoglycoside-resistant isolates and screened by PCR for β-lactamase genes (blaTEM, blaCTX-M, blaSHV) and aminoglycoside-modifying enzyme genes (aac(6')-Ib, ant(4')-Ia, aph(3')-IIIa). Bacterial growth was obtained from 208/224 (92.9%) samples; six species were recovered: Staphylococcus aureus 41.3% (86/208), Escherichia coli 20.2% (42/208), Staphylococcus epidermidis 12.5% (26/208), Proteus vulgaris 10.6% (22/208), Proteus mirabilis 7.7% (16/208) and Pseudomonas aeruginosa 7.7% (16/208). Resistance to gentamicin was uniformly high (S. aureus 91.9%; E. coli 90.5%; S. epidermidis 84.6%); cefoperazone-sulbactam was the most active β-lactam against S. aureus (43.0% resistance) and colistin retained activity against E. coli (35.7% resistance). PCR detected aac(6')-Ib in 114/208 (54.8%), blaTEM in 91/208 (43.8%), blaCTX-M in 83/208 (39.9%), blaSHV in 82/208 (39.4%), ant(4')-Ia in 78/208 (37.5%) and aph(3')-IIIa in 76/208 (36.5%) of isolates. Fisher's exact test confirmed strong, statistically significant associations between aminoglycoside-modifying enzyme genes and gentamicin resistance, and between β-lactamase genes and cefotaxime resistance (specificity and positive predictive value = 100% at the reference antibiotic). DFUs in this Pakistani cohort were predominantly polymicrobial with a high burden of plasmid-mediated β-lactam and aminoglycoside resistance determinants. Strengthened antimicrobial stewardship, expanded molecular surveillance and patient-centred foot-care education are critical to reduce amputation risk and the public-health burden of DFU.
    Keywords:  Aminoglycoside-modifying enzymes; Antimicrobial resistance; Diabetes mellitus; Diabetic foot ulcer; Plasmid-mediated resistance; β-lactamase
    DOI:  https://doi.org/10.1038/s41598-026-61198-y
  59. mSphere. 2026 Jul 06. e0038626
      Metagenomic data provide evidence that bacteriophage (phage) abound in the enteric microbiomes of humans. However, the contribution of these viruses in shaping the bacterial composition of the gut microbiome and how these phages are maintained remain unclear. We performed experiments with 756 combinations of 54 Escherichia coli and nine phage isolates from four fecal microbiota transplantation (FMT) doses and five laboratory phages as samples of non-dysbiotic human enteric microbiota. We also developed a mathematical model of the population and evolutionary dynamics of bacteria and phage. Our experiments predict that as a consequence of the production of the O antigen, most of the E. coli in the human enteric microbiome will be resistant to infections with the array of co-occurring phages. Our modeling suggests that phages are maintained in these enteric communities due to the high rates of transition between the O antigen-resistant and -sensitive states. Based on our observations and predictions from this theory, we postulate that the phage found in the human gut are likely to play a little role in shaping the strain composition of E. coli of healthy individuals. Although we only investigated E. coli, the mechanism of resistance described here is shared among most of the gram-negative bacteria. Evidence is provided that, as a consequence of O antigen-mediated resistance, the genetically diverse array of bacteriophage in the gut microbiome of humans plays little or no role in determining the densities and distribution of the genetically diverse strain E. coli in this habitat. Our mathematical model predicts and our experiments support the hypothesis that the phage present in the gut microbiome are maintained by replication on the minority of sensitive bacteria generated by the leakiness of O antigen-mediated resistance.IMPORTANCEBacteriophages (phages) are abundant in the human gut, yet whether these viruses shape the bacterial communities living there remains unresolved. Using Escherichia coli and phages isolated from the stool of healthy fecal microbiota transplantation (FMT) donors, together with a mathematical model, we show that the vast majority of gut E. coli are resistant to co-occurring phages because they express the O antigen, a surface structure that masks the receptors phages use to attach. Despite this widespread resistance, phages persist by replicating on a small, continually regenerated subpopulation of sensitive cells, a phenomenon we term leaky resistance. These findings suggest that phages play a little role in determining which E. coli strains dominate the healthy human gut. Because the O antigen is broadly expressed across gram-negative bacteria, this mechanism likely extends well beyond E. coli and helps explain why isolating therapeutic phages against many pathogens is difficult.
    Keywords:  Escherichia coli; bacteriophage; enteric microbiome; fecal microbiota transplantation; phage resistance; population biology
    DOI:  https://doi.org/10.1128/msphere.00386-26
  60. Probiotics Antimicrob Proteins. 2026 Jul 07.
      Amidst the rising antimicrobial resistance in hypervirulent Klebsiella pneumoniae (hvKP), phage therapy has emerged as a promising alternative. However, bacterial resistance to phages remains a critical challenge, with virulence attenuation representing a key characteristic of phage-resistant strains, albeit through incompletely elucidated mechanisms. This study investigated the phage-host interaction between phage vB_LZ2044 and hvKP strain NTUH-K2044, yielding a phage-resistant mutant PR_K2044. Comparative analysis revealed marked virulence attenuation in PR_K2044, accompanied by significant alterations in virulence-associated phenotypes, including capsular polysaccharide (CPS) production, lipopolysaccharide (LPS) integrity, urea metabolism, biofilm formation, and siderophore activity. Whole-genome sequencing (WGS) identified a singular nonsynonymous mutation (Ser332Leu) in the capsular synthesis regulator WcaJ. Transcriptomic analysis demonstrated coordinated regulation of multiple virulence-associated genes, including: CPS related genes (magA, wza, wzb, wzc, gnd, ugd, manB), LPS related genes (glf, wbbN, wbbO, wbbM, wzt, wabH), pili related genes (fimA, mrkC), outer membrane protein associated genes (ompA, acrB), nitrogen metabolism related genes (gcl, hyi, glxR, allB, allC, ureA), biofilm related gene fabZ and siderophore related gene ybtS. Our investigation integrating genomic, transcriptomic, and phenotypic analyses elucidates potential mechanisms underlying virulence attenuation and coordinated reprogramming in phage-resistant hvKP, providing critical insights for optimizing phage-based therapeutic strategies against multidrug-resistant pathogens and underscoring the need to consider adaptive trajectories when evaluating the therapeutic promise and evolutionary consequences of phage therapy.
    Keywords:  Hypervirulent Klebsiella pneumoniae ; Phage resistance; Virulence
    DOI:  https://doi.org/10.1007/s12602-026-11133-4
  61. Front Chem. 2026 ;14 1842082
      Faced with a severe outbreak of diseases caused by newly emerging and recurrent pathogens, the development cycle of traditional drugs is long, making it difficult to meet emergency needs. Drug repositioning has become a key strategy for rapidly providing therapies by exploring new therapeutic uses of approved drugs. However, traditional reposition methods have bottlenecks such as slow speed and strong randomness. Artificial intelligence (AI) is revolutionizing drug reposition by analyzing and integrating multi-source data with computational models, dramatically accelerating the discovery process. This article summarizes the core technological approaches of AI-driven drug reposition, including predictions based on network medicine, virtual screening through deep learning models, and association discovery via real-world data mining. Multiple successful cases are presented to verify their effectiveness. Although there are still challenges in terms of data quality, model interpretability, and clinical translation, AI will undoubtedly reshape our drug development paradigm for addressing future public health crises, serving as a pivotal engine for rapid response and precise intervention.
    Keywords:  AI-driven; alphafold 3 (AF3); deep integrated network analysis (DINA); drug repositioning; infectious diseases
    DOI:  https://doi.org/10.3389/fchem.2026.1842082