bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2026–08–02
sixty-two papers selected by
Luca Bolliger, lxBio



  1. Front Cell Infect Microbiol. 2026 ;16 1891884
      Diabetic foot ulcers (DFUs) are a serious diabetes-related complication characterized by high rates of amputation and mortality. Emerging evidence suggests that DFUs are not simply the result of infection, but also involve microbiome dysbiosis, which impairs healing. Systemically, disturbances to the gut microbiota via the gut-skin axis promote systemic inflammation and metabolic dysfunction. Locally, skin microbial diversity is significantly reduced, allowing opportunistic pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa to form resilient biofilms. These biofilms resist antibiotics and host immunity, while microbial virulence factors exacerbate tissue damage and disrupt the healing cascade. This synergy between host pathology and dysbiosis perpetuates chronic ulceration. Novel therapeutic strategies therefore aim to modulate this aberrant ecology by shifting from broad-spectrum eradication to targeted restoration. Promising approaches include probiotics, phage therapy, traditional Chinese medicine, and faecal microbiota transplantation, which seek to recalibrate the microbiome and promote healing. However, translation into clinical practice requires more robust evidence from large-scale trials. Future perspectives point towards personalized microbial medicine, integrating multi-omics data and artificial intelligence to match interventions with specific microbial ecotypes, which may reduce the global burden of DFUs.
    Keywords:  artificial intelligence; biofilm; diabetic foot ulcer; gut-skin axis; microbiome dysbiosis; phage therapy
    DOI:  https://doi.org/10.3389/fcimb.2026.1891884
  2. mBio. 2026 Jul 30. e0325425
      Bacteriophages (phages) are the viral predators of bacteria. Their ability to infect and kill bacterial strains has been harnessed for use in clinical practice for more than a century, but their development stalled for decades in many regions. Now, in the face of increasingly complex bacterial infections that fail conventional therapeutic options, and the growing global threat of antibiotic resistance, interest in phage therapy has resurged. Data evaluating the impact of phage therapy via clinical trials are steadily increasing, but remain sparse. Yet, an ever-growing number of case reports and case series highlights the potential of phage therapy to make a positive impact in the battle against antimicrobial resistance and difficult-to-treat bacterial infections. In this review, we summarize the available data describing the clinical utility of phage therapy, highlight infectious indications where phage therapy shows strong potential, and call attention to disease states where the benefits of phage therapy, as it is practiced today, are less certain. Furthermore, we note areas where there is a crucial need for additional research and propose how scientists and clinicians can work together to design and carry out the preclinical and clinical studies that will take phage therapy into its next century.
    Keywords:  antibiotic resistance; bacterial infections; phage therapy
    DOI:  https://doi.org/10.1128/mbio.03254-25
  3. Antibiotics (Basel). 2026 Jun 25. pii: 635. [Epub ahead of print]15(7):
      Antimicrobial resistance and persistent biofilm-associated infections have renewed interest in bacteriophages as alternatives or complements to conventional antibiotics. However, broader therapeutic adoption remains constrained by slow phage discovery, incomplete genome characterization, narrow host range, complex therapeutic matching, and manufacturing variability. Artificial intelligence (AI) offers computational approaches that may help address several of these limitations. This comprehensive narrative review discusses current AI applications across the bacteriophage pipeline, including metagenomic phage discovery, genome annotation, phage-host interaction prediction, personalized phage selection, cocktail optimization, and phage-antibiotic combination design. The review also examines AI-assisted synthetic biology approaches, including receptor-binding protein redesign, CRISPR-enabled engineering, generative genome design, and biosafety screening, as well as emerging applications in bioprocess optimization, yield prediction, purification analytics, quality assurance, and supply-chain management. Current evidence suggests that AI may accelerate phage identification, improve host-range prediction, support therapeutic optimization, and strengthen manufacturing consistency, potentially facilitating the transition of phage therapy from individualized rescue interventions toward more scalable antimicrobial platforms. Nevertheless, major limitations remain, including fragmented, taxonomically biased datasets; limited external validation; restricted interpretability; privacy concerns; biosafety oversight; and evolving regulatory frameworks. Future progress will depend on standardized datasets, multimodal validation, scalable manufacturing systems, experimental and clinical verification, and coordinated regulatory development.
    Keywords:  antimicrobial resistance; genome annotation; machine learning; phage optimization; synthetic biology
    DOI:  https://doi.org/10.3390/antibiotics15070635
  4. Acta Chir Orthop Traumatol Cech. 2026 Jul;93(3): 170-177
      Bacteriophage therapy has re-emerged as a potential adjunctive strategy in the management of orthopedic and trauma-related infections, particularly fracture-related infection (FRI) and periprosthetic joint infection (PJI). These conditions are associated with biofilm formation, repeated surgery, prolonged antimicrobial therapy, impaired functional outcomes, and increasing rates of multidrug-resistant pathogens. The therapeutic rationale of bacteriophages is based on their high specificity for target bacteria, their ability to replicate at the site of infection, and their potential activity against biofilm. Experimental studies have demonstrated reduced bacterial burden, biofilm disruption, and improved efficacy of combined phage-antibiotic treatment. Progress made in local delivery systems and rapid diagnostic methods facilitates the development of personalized phage-based approaches. Nevertheless, current clinical evidence remains limited and largely derives from case reports and small series. Although preliminary results are encouraging, the role of bacteriophage therapy in routine orthopedic practice has not yet been established. At present, bacteriophage therapy should be regarded as an individualized adjunctive treatment option rather than an established standard of care for PJI and FRI.
    Keywords:  FRI; PJI; antimicrobial resistance; bacteriophage therapy; biofilm-associated infection; implant-associated infection; local treatment.; orthopedic surgery
    DOI:  https://doi.org/10.55095/achot2026/018
  5. J Clin Lab Anal. 2026 Jul 28. e70293
       INTRODUCTION: Burn wound infections caused by Acinetobacter baumannii remain a critical clinical challenge due to its extensive multidrug resistance, particularly against carbapenems. The growing ineffectiveness of conventional antibiotics has encouraged the exploration of biological alternatives with improved safety and efficacy.
    AIMS: This review summarizes current insights into the pathogenic mechanisms of A. baumannii in burn wounds and evaluates the therapeutic potential of bacteriophages and probiotics as emerging nonantibiotic interventions.
    METHODS: Data from the four international information databases Medline, Scopus, Embase, and Google Scholar. The search strategy was based on the combination of the following terms: "Acinetobacter baumannii," "Burn wound infections," "bacteriophages," "probiotics," "Multidrug resistance Acinetobacter baumannii," and "synergism".
    RESULT: Phages offer highly specific antibacterial activity against resistant strains, while probiotics exert antimicrobial, immunomodulatory, and wound-healing properties. Integrating findings from recent in vitro, in vivo, and clinical studies.
    DISCUSSION: This review highlights the synergistic potential of combined phage-probiotic strategies in controlling infection, reducing bacterial load, and promoting tissue repair.
    CONCLUSION: These approaches represent promising next-generation therapies for managing multidrug-resistant A. baumannii infections in burn patients.
    Keywords:   Acinetobacter baumannii ; biological treatment; multidrug resistance; phage therapy; probiotics; wound healing
    DOI:  https://doi.org/10.1002/jcla.70293
  6. Nat Commun. 2026 07 27. pii: 7411. [Epub ahead of print]17(1):
      Ventilator-associated infections (VAIs) caused by multidrug-resistant (MDR) pathogens poses a significant challenge in intensive care units (ICUs). Phage therapy has emerged as a promising alternative for VAIs, though its efficacy depends on multiple factors. We report a 40-year-old male ICU patient with sequential pulmonary infections of MDR Acinetobacter baumannii, Klebsiella pneumoniae, and Stenotrophomonas maltophilia. Seven rounds of tailored phage therapy-targeting single or dual pathogens-were administered adjunctive to antibiotics. A. baumannii was complete eradication, but K. pneumoniae and S. maltophilia showed cyclical clearance and recurrence due to strain replacement and phage resistance. Phage therapy correlated with reduced bacterial load, fever, procalcitonin, and IL-6 levels, alongside improved pulmonary inflammation, while white blood cell counts and C-reactive protein showed limited response. No severe adverse events occurred. Dynamic shifts in dominant pathogens aligned with clinical progression, with phage therapy providing transient control, extending the window for intervention and reducing high-level antibiotic use. After six months, the patient was weaned from ventilation and discharged. This case underscores the complexity of VAI management and highlights the potential of personalized phage therapy to mitigate MDR infections and minimize antibiotic reliance. This case was enrolled in a single arm trial (ChiCTR2000036801).
    DOI:  https://doi.org/10.1038/s41467-026-75735-w
  7. J Bone Joint Surg Am. 2026 Jul 28.
      ➢ Periprosthetic joint infection (PJI) remains the most common cause of failure after total joint arthroplasty, with current standard therapies associated with failure rates between 10% and 30%.➢ The 2025 International Consensus Meeting in Istanbul, Türkiye, highlighted the potential benefits of bacteriophage (phage) therapy in managing PJI.➢ One of the barriers to integrating phage therapy into standard clinical PJI care is the knowledge gap between preclinical research and clinical practice.➢ This Expert Review summarizes the key therapeutic advantages of using phages as an adjuvant therapeutic platform for PJI. It also highlights the current challenges that are continuing to limit the integration of phages into standard PJI care.
    DOI:  https://doi.org/10.2106/JBJS.26.00339
  8. Comb Chem High Throughput Screen. 2026 Jul 21.
       INTRODUCTION: Medicinal plants are increasingly recognized as alternative and complementary therapies, particularly in India and other Asian countries. Tinospora cordifolia (Giloy/Guduchi) is a well-known medicinal plant with extensive therapeutic applications, including immune modulation, antidiabetic, anti-inflammatory, antioxidant, and antimicrobial effects. Given these properties, T. cordifolia shows promise for managing Diabetic Foot Ulcers (DFUs), a severe complication of diabetes associated with infection and the risk of amputation.
    METHODS: This review compiles and critically analyzes the published literature on T. cordifolia, focusing on its phytochemical composition, pharmacological activities, and therapeutic relevance to diabetic foot ulcers. Data were gathered from PubMed, Scopus, Web of Science, and Google Scholar, including experimental, preclinical, and clinical studies describing its bioactive constituents and mechanisms related to immune regulation and wound healing.
    RESULTS: Bioactive compounds such as alkaloids, diterpenoids, and polysaccharides derived from the stem, root, and whole plant exhibit significant immunomodulatory, anti-inflammatory, antioxidant, and antibacterial activities. These properties collectively support enhanced wound healing, infection control, and immune regulation, indicating the potential effectiveness of T. cordifolia in the treatment of DFU. Its favorable physiological compatibility and minimal side effects further strengthen its therapeutic value.
    DISCUSSION: The multifaceted pharmacological actions of T. cordifolia align well with the complex pathophysiology of diabetic foot ulcers, which involves impaired immunity, chronic inflammation, oxidative stress, and microbial infection. The plant's immune-modulating and wound-healing effects suggest its usefulness as an adjunct to conventional DFU therapies. However, mechanistic insights and standardized clinical evidence remain limited.
    CONCLUSION: Tinospora cordifolia represents a promising adjunctive therapeutic option for the management of diabetic foot ulcers. Future research should emphasize detailed biochemical mechanisms, synergistic effects with conventional drugs or other herbs, and well-designed clinical trials. Its incorporation into nutraceuticals and dietary supplements may further aid in chronic disease management and immune enhancement, bridging traditional knowledge with modern therapeutic strategies.
    Keywords:  Diabetic foot ulcer; antioxidant; diabetes.; immunomodulation; wound healing property
    DOI:  https://doi.org/10.2174/0113862073448681260703192723
  9. Children (Basel). 2026 Jun 30. pii: 878. [Epub ahead of print]13(7):
      Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Recently developed effective CFTR modulator drugs have substantially altered the disease trajectory of people with CF (pwCF) with access to these new therapies. Yet globally, this transformation to causal treatment remains profoundly unequal, with a substantial proportion of pathogenic CFTR variants in populations of non-European ancestry neither detectable by widely used genetic CF screening panels nor approved for or responsive to modulator therapies. This narrative review organizes the current global treatment realities along three axes: pwCF with access to CFTR modulator therapy; pwCF experiencing structural barriers in proper diagnosis and drug access; and those pwCF with biological realities not predisposing to currently approved effective CF drugs.
    Keywords:  CFTR modulators; HEMT; cystic fibrosis; diagnostic disparities; drug access; genetic epidemiology; global health equity; low- and middle-income countries; newborn screening
    DOI:  https://doi.org/10.3390/children13070878
  10. Metabolites. 2026 Jul 16. pii: 502. [Epub ahead of print]16(7):
      Periodontitis is a chronic inflammatory disease increasingly recognized as a manifestation of complex microbial dysbiosis extending beyond the oral cavity. Recent advances in spatial metagenomics provide unprecedented resolution to investigate microbial community structure, function, and localization within periodontal niches and along the oral-gut axis. This review aims to explore how spatially resolved metagenomic approaches refine our understanding of the ecological and functional shifts in bacterial populations associated with periodontitis and their systemic implications. By integrating spatial mapping with shotgun metagenomics, we highlight distinct microenvironmental signatures within periodontal pockets, characterized by anaerobic pathobionts, metabolic reprogramming, and localized inflammatory gradients. Furthermore, we examine evidence supporting bidirectional interactions between oral and gut microbiota, suggesting that oral-derived taxa may contribute to gut dysbiosis through translocation and ecological disruption. From a basic science perspective, spatial metagenomics reveals niche-specific microbial functions and interspecies interactions that are not captured by bulk sequencing. Clinically, these insights open avenues for precision diagnostics and targeted therapeutics, including microbiome modulation strategies tailored to spatial microbial organization. Overall, this work underscores the importance of spatial context in metagenomic analyses and advances the conceptual framework linking periodontal disease to systemic microbial dysbiosis.
    Keywords:  bulk sequencing; dysbiosis; metagenomics; microbiome; oral biofilm; oral–gut axis; periodontitis; spatial mapping; spatial metagenomics
    DOI:  https://doi.org/10.3390/metabo16070502
  11. Genes (Basel). 2026 Jun 27. pii: 743. [Epub ahead of print]17(7):
      Cystic fibrosis (CF) is an autosomal recessive disorder caused by pathogenic variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. It is increasingly understood through a genomics-informed framework linking variant architecture to phenotype, diagnosis, and therapeutic eligibility. This review summarizes current evidence on CFTR structure, variant interpretation, genotype-phenotype heterogeneity, diagnostic workflows, and modern management. We highlight how full-gene sequencing, curated disease-liability databases, functional testing, and organoid-informed theratyping refine diagnosis and treatment selection; how disrupted chloride and bicarbonate transport drives muco-obstructive airway disease and multisystem complications; and why modulator therapy must still be integrated with respiratory, nutritional, endocrine, hepatobiliary, reproductive, and psychosocial care. We also outline unresolved challenges in rare variants, residual organ damage, ancestry-related diagnostic gaps, and mutation-agnostic therapeutic development.
    Keywords:  CFTR; CFTR modulators; cystic fibrosis; genomic diagnostics; genotype–phenotype correlation; precision medicine; variant interpretation
    DOI:  https://doi.org/10.3390/genes17070743
  12. Zhonghua Yi Xue Za Zhi. 2026 Jul 28. 106(27): 2883-2886
      Diabetic foot is a common condition that imposes a substantial burden on patients and society. Although prolonged activity restriction in traditional management may facilitate ulcer healing, it is detrimental to overall health. Therefore, a balance must be achieved between promoting wound healing and preserving mobility. Offloading and immobilization constitute the core principles of diabetic foot management. Offloading reduces wound stress by redistributing plantar pressure, whereas immobilization promotes local healing by limiting joint motion. To effectively balance these two therapeutic principles, the medical team led by German physicians Dirk Hochlenert and Gerald Engels has accumulated extensive clinical experience through years of clinical practice combining FiF!mobil® felt padding with non-removable offloading orthoses. This article elaborates on the core concepts of pressure offloading and immobilization with targeted clinical examples. The introduced protective devices are structural components designed to redistribute abnormal plantar pressure points without inducing secondary tissue damage, enabling standardized clinical implementation. Given the limited nationwide adoption of this technique in China, our research team co-authored this paper with the aforementioned German specialists to introduce this integrated therapeutic regimen, provide standardized training protocols and practical tools for clinicians, and facilitate continuous improvement in the prevention and management of diabetic foot disease.
    DOI:  https://doi.org/10.3760/cma.j.cn112137-20251217-03335
  13. Antonie Van Leeuwenhoek. 2026 Jul 25. pii: 174. [Epub ahead of print]119(8):
      Bacterial immune systems encompass the multi-layered defense mechanisms that bacteria develop against bacteriophages and mobile genetic elements, such as plasmids. This review covers bacterial innate defense systems (surface defenses, superinfection exclusion, restriction-modification, abortive infection, and toxin-antitoxin systems), CRISPR-Cas-mediated adaptive immunity, and the escape strategies used by phages to overcome these defenses (genome modifications, anti-restriction proteins, and anti-CRISPR factors). Emerging evidence also highlights the role of outer membrane vesicles (OMVs) in anti-phage defense and their translational potential as vaccine and delivery platforms. In this context, a better understanding of bacterial defense systems contributes to the development of biotechnology and medical applications such as CRISPR technologies, diagnostic approaches, and phage therapy.
    Keywords:  Abortive infection; Anti-CRISPR proteins; Bacterial immunity; Bacteriophage; CRISPR-Cas systems; Outer membrane vesicles; Phage resistance; Restriction-modification systems; Toxin-antitoxin systems
    DOI:  https://doi.org/10.1007/s10482-026-02373-z
  14. Acta Parasitol. 2026 Jul 27. pii: 172. [Epub ahead of print]71(4):
       PURPOSE: Cutaneous leishmaniasis (CL) is a vector-borne parasitic disease characterized by chronic skin lesions. Emerging evidence has highlighted the critical role of the skin microbiome and bacterial biofilms in disease progression. This review discusses the current evidence supporting the involvement of the skin microbiome and bacterial biofilms in the pathogenesis of CL. It further examines the clinical significance of microbiota dysbiosis and bacterial coinfections, reviews emerging biofilm-directed adjunctive therapeutic strategies, and outlines key knowledge gaps for future translational research.
    METHODS: The available literature on the skin microbiome, bacterial biofilms, microbiota dysbiosis, bacterial coinfections, host immune responses, and emerging biofilm-directed adjunctive therapeutic strategies in cutaneous leishmaniasis was reviewed.
    RESULTS: CL lesions are associated with microbial dysbiosis characterized by an increased abundance of opportunistic bacteria including Staphylococcus and Streptococcus species. These alterations contribute to dysregulated host immune responses, including increased production of pro-inflammatory cytokines and enhanced neutrophil recruitment, thereby promoting disease progression and delaying wound healing. Biofilm formation within CL lesions represents an additional factor contributing to disease persistence. Biofilms protect bacteria from host immune defences and limit antimicrobial penetration, thus reducing therapeutic efficacy and contributing to treatment failure. The interplay among Leishmania, bacterial communities, and host immunity creates a complex polymicrobial microenvironment that exacerbates lesion pathology.
    CONCLUSION: A deeper understanding of these complex interactions may enable the design of more effective therapeutic approaches directed at both the parasite and the polymicrobial wound environment.
    Keywords:  Bacterial biofilm; Cutaneous leishmaniasis; Microbiota dysbiosis; Skin microbiome
    DOI:  https://doi.org/10.1007/s11686-026-01353-7
  15. Microbiology (Reading). 2026 Jul;172(7):
      Pseudomonas aeruginosa is commonly isolated from chronic wounds where it forms biofilms that are recalcitrant to current treatments, greatly impacting the morbidity and mortality of infected patients. Since P. aeruginosa dictates wound severity and treatment outcomes, this bacterium is an important target in the treatment of chronic wound infections. This study aimed to unravel the functional intricacies of a key virulence factor, the arginine-specific aminopeptidase of P. aeruginosa (AaaA), which is crucial for the establishment and persistence of chronic infections. While interrogation of genomes revealed that aaaA is highly conserved, its activity varied between chronic wound clinical isolates. To explore the phenotypic impact of AaaA in chronic infections, a collagen-based synthetic chronic wound (SCW) model was optimized to enable reproducible assessment of AaaA activity. AaaA activity was increased within the SCW compared to planktonic cultures, further supporting the hypothesis that this virulence factor is integral to chronic infections caused by P. aeruginosa. It was also shown that AaaA contributed to biofilm formation as well as providing a survival advantage within the SCW model. Overall, a novel link between AaaA and biofilm formation was verified and served to guide the optimisation of a realistic chronic wound infection model.
    Keywords:  arginine; biofilms; chronic wound; clinical isolates; virulence
    DOI:  https://doi.org/10.1099/mic.0.001719
  16. J Appl Microbiol. 2026 Jul 25. pii: lxag190. [Epub ahead of print]
       AIMS: This study aimed to evaluate whether combining phages with different properties enhances antibacterial efficacy against individual strains and enables the simultaneous control of multiple bacterial species belonging to different genera.
    METHODS AND RESULTS: Our phage collection was screened for phages active against Aeromonas hydrophila, Escherichia coli, Salmonella enterica Typhimurium and Vibrio parahaemolyticus. Four phages were selected: AH-1, ECA2, phSE-5 and vB_VpS_LMAVpSH, originally isolated using A. hydrophila, S. Typhimurium, E. coli and V. parahaemolyticus as hosts, respectively. An initial phage cocktail (CK3) was prepared excluding phage SH, which was later included in a modified cocktail (CK4). Phage efficacy was evaluated in vitro (in nutrient-rich media and synthetic seawater) against bacterial strains individually and against mixed cultures of the four bacteria, for 12 h at 25°C. Both cocktails were associated with greater bacterial reduction compared with individual phage treatments, alongside reduced bacterial regrowth under the tested conditions. Although efficacy decreased in nutrient-limited conditions, phages still inhibited bacterial growth.
    CONCLUSIONS: The findings of this study provide experimental evidence of phage-bacteria interactions in multispecies systems and offer proof-of-concept evidence supporting further evaluation of phage cocktail approaches under aquaculture-relevant conditions.
    Keywords:  Bacteriophages; Multiple bacterial species; Phage infection; Phage resistance
    DOI:  https://doi.org/10.1093/jambio/lxag190
  17. Vet Clin North Am Small Anim Pract. 2026 Jul 29. pii: S0195-5616(26)00085-9. [Epub ahead of print]
      S pseudintermedius is a leading cause of canine pyoderma and an important pathogen in small animal skin, soft tissue, otic, wound, and postoperative infections. The emergence of methicillin-resistant S pseudintermedius (MRSP) has made recurrent infections more difficult to manage by combining multidrug resistance, biofilm-associated persistence, treatment failure, and repeated antimicrobial exposure. This article reviews MRSP emergence and epidemiology, mechanisms of resistance and recurrence, and the limitations of current treatment options. It discusses emerging therapeutic strategies, including phage-based therapies, microbiome-directed interventions, immune modulation, nanomaterials, photodynamic therapy, and antimicrobial peptides, that serve as adjuncts to standard care and reduce reliance on systemic antimicrobials.
    Keywords:  Antimicrobial resistance; Antimicrobial stewardship; Biofilm; Emerging therapeutics; MRSP; Multidrug resistance; Staphylococcus pseudintermedius
    DOI:  https://doi.org/10.1016/j.cvsm.2026.06.004
  18. Microorganisms. 2026 Jul 15. pii: 1551. [Epub ahead of print]14(7):
       BACKGROUND: Recent scientific evidence indicates that the oral-gut axis represents a critical interface in host-microbiota interactions, carrying profound implications for both periodontal and gastrointestinal diseases. This scoping review aims to evaluate the reciprocal influence between periodontitis and inflammatory bowel disease (IBD). Specifically, the underlying mechanisms of microbial translocation, immune interaction, and metabolite-mediated signaling linking the oral microbiota to gut microbial ecology are critically evaluated.
    METHODS: Studies were selected from the PubMed, Web of Science, and Scopus databases up to May 2026. Eligible criteria included in vivo studies written in English and conducted within the last 10 years, whereas human studies involving participants under 18 years of age were excluded. The included studies analyze the effects of oral and gut dysbiosis on the opposing district. Through the database search, 2094 records were identified, and 34 articles were selected based on the eligibility criteria.
    RESULTS: The included studies demonstrate the interconnection between the oral and gut microbiota. The included studies reveal that predominant oral taxa, specifically Porphyromonas gingivalis, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans, alter intestinal microbial composition. In particular, P. gingivalis colonizes the gut, exacerbating both oral and intestinal inflammation by stimulating pro-inflammatory cytokine expression via Th17 cell activation. Finally, salivary microbial composition appears to be associated with the presence and status of IBD.
    CONCLUSIONS: Understanding these interconnected microbial ecosystems provides valuable insights that may support the future development of integrated diagnostic and therapeutic strategies for patients suffering from periodontitis and IBD. Further large-scale studies with longer follow-up periods are required to standardize potential salivary markers and multidisciplinary therapeutic protocols for the management of periodontitis and IBD.
    Keywords:  Crohn’s disease; dysbiosis; gut microbiota; inflammatory bowel disease; oral microbiota; periodontitis; saliva; ulcerative colitis
    DOI:  https://doi.org/10.3390/microorganisms14071551
  19. Antibiotics (Basel). 2026 Jul 03. pii: 659. [Epub ahead of print]15(7):
      Background: Cutibacterium avidum is an emerging opportunistic pathogen responsible for device-associated infections, including prosthetic joint and breast implant infections. Unlike its relative C. acnes, for which phage therapy has been explored, C. avidum infections are recalcitrant to antibiotics, and no infecting bacteriophages have been described to date. Here, we report the isolation and characterization of ΦCA1NRNZ, to the best of our knowledge, the first lytic phage described against C. avidum. Methods: ΦCA1NRNZ was obtained from wastewater sampling at the Sorek Treatment Facility in Jerusalem. Wastewater metagenomics, transmission electron microscopy, genome sequencing, host-range testing, efficiency of plating (EOP), aerobic and anaerobic lysis assays, and antibiofilm assays against mature C. avidum biofilms were performed. Results: Metagenomic analysis indicated low and transient detection of C. avidum-classified reads in wastewater. ΦCA1NRNZ was identified as a long-tailed Caudoviricetes with a ~320 nm virion. Its 33,712 bp dsDNA genome (GenBank PV441878.1) encodes 46 predicted proteins, shares 76.5% nucleotide identity with C. acnes phage ΦFD1, and contains divergent tail-fiber and host-recognition genes. No known bacterial virulence, toxin, human pathogenicity-associated, or antibiotic-resistance genes were identified. ΦCA1NRNZ lysed all 11 clinical C. avidum isolates tested under aerobic and anaerobic conditions, with EOP values of 0.11-5.55, mean 1.87, and showed no lytic activity against 25 C. acnes isolates. Against mature biofilms, ΦCA1NRNZ reduced total biomass by 28.4% (p = 0.014), reduced viable cell counts by approximately two logs, and increased extracellular ATP release (p < 0.001). Conclusions: The strict species specificity and significant in vitro antibiofilm activity of ΦCA1NRNZ support its potential for phage therapy of device-associated C. avidum infections.
    Keywords:  Cutibacterium avidum; biofilm inhibition; phage therapy
    DOI:  https://doi.org/10.3390/antibiotics15070659
  20. Ther Clin Risk Manag. 2026 ;22 602768
       Purpose: Diabetic foot ulcers represent a major clinical challenge due to delayed healing and high risk of complications. Medicinal encircling therapy, a traditional external treatment, has been widely used as an adjunctive intervention in clinical practice. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of medicinal encircling therapy combined with conventional treatment for diabetic foot ulcers.
    Material and Methods: A comprehensive literature search was conducted across major English and Chinese databases from inception to November 1, 2025. Randomized controlled trials comparing medicinal encircling therapy plus conventional care versus conventional care alone were included. Primary and secondary outcomes related to ulcer healing, symptom improvement, inflammatory markers, pain, and adverse events were synthesized using risk ratios or mean differences with corresponding 95% confidence intervals. This systematic review was prospectively registered with PROSPERO (CRD420261299230).
    Results: Fifteen randomized controlled trials were included, all of which were published in Chinese. The pooled results showed that adjunctive medicinal encircling therapy significantly improved complete ulcer healing rate compared with conventional treatment alone (RR = 1.78, 95% CI 1.39-2.28). Overall clinical response and several secondary outcomes generally favored the intervention, although heterogeneity was observed for some outcomes. No serious treatment-related adverse events were reported.
    Conclusion: These findings suggest that medicinal encircling therapy may be a promising adjunctive treatment for diabetic foot ulcers; however, the certainty and generalizability of the evidence are limited by methodological shortcomings, incomplete safety reporting, and the inclusion of Chinese-language studies only. Further high-quality, multicenter randomized controlled trials are warranted.
    Keywords:  diabetic foot ulcer; medicinal encircling therapy; meta-analysis; systematic review; wound healing
    DOI:  https://doi.org/10.2147/TCRM.S602768
  21. Mol Med Rep. 2026 Oct;pii: 263. [Epub ahead of print]34(4):
      Periodontitis, a common oral disease, is increasingly recognized for its potential impact on systemic health, particularly its association with heart failure (HF). HF is a complex clinical syndrome with a multifactorial pathogenesis. Emerging evidence suggests that periodontitis may influence the cardiovascular system and contribute to the onset and progression of HF through mechanisms such as systemic inflammation, microbial shifts, and immune dysregulation. However, current research still faces limitations in establishing causality and elucidating the precise underlying mechanisms. Furthermore, clinical intervention strategies require further investigation. Relevant literature was identified from PubMed, Web of Science, and Scopus using keywords related to periodontitis and heart failure, and screened for relevance to epidemiological evidence, mechanistic insights, and clinical implications. The present review aimed to summarize the mechanisms linking periodontitis and HF, analyze their shared pathophysiological basis, and discuss the potential role of periodontal treatment in improving outcomes for patients with HF. Clinically, periodontal assessment may be considered in patients with heart failure as part of multidisciplinary care, but current evidence remains insufficient to support definitive recommendations that such evaluation or treatment improves HF outcomes.
    Keywords:  cardiovascular disease; heart failure; inflammation; microbiome; periodontitis
    DOI:  https://doi.org/10.3892/mmr.2026.13974
  22. Arch Microbiol. 2026 Jul 30. pii: 524. [Epub ahead of print]208(10):
      Typhoid fever, caused by Salmonella enterica subsp. enterica serovar Typhi (Salmonella Typhi), remains a significant global health challenge that is increasingly complicated by the emergence and spread of multidrug-resistant (MDR) and extensively drug-resistant strains. Growing limitations of antibiotic-centered treatment strategies have stimulated interest in anti-virulence approaches targeting bacterial regulatory networks rather than viability alone. Among these, quorum-sensing (QS), particularly the LuxS-mediated autoinducer-2 (AI-2) signaling system, has emerged as a potential regulator of virulence-associated phenotypes, biofilm formation, stress adaptation, microbial communication, and host-associated persistence. This review critically evaluated the current understanding of QS biology in S. Typhi while distinguishing experimentally validated findings from evidence extrapolated from non-typhoidal Salmonella and other enteric bacteria. We examine the ecological interplay between QS, gut microbiome dynamics, and host responses, highlighting how microbial communication networks influence pathogen adaptation and colonization resistance. Emerging anti-QS strategies, including microbiome-mediated quorum quenching, probiotics, postbiotics, phytochemicals, antimicrobial peptides, bacteriophage-associated approaches, signal-degrading enzymes, and nucleic acid-based interventions, are comparatively assessed with respect to their mechanisms, evidence strength, translational readiness, and limitations. The review further explores the role of artificial intelligence (AI), multi-omics integration, and systems-level analytical frameworks in target identification, microbial network reconstruction, biomarker discovery, and therapeutic prioritization. Despite promising advances, substantial barriers remain, including limited in vivo validation, insufficient mechanistic evidence in S. Typhi, lack of clinically validated QS-associated biomarkers, microbiome variability, ecological safety concerns, and challenges related to delivery, scalability, and regulatory approval. Collectively, current evidence supports QS-targeted interventions as promising but predominantly investigational strategies that may complement existing antimicrobial, vaccine-based, and public-health approaches for typhoid control.
    Keywords:  Anti-virulence therapeutics; Artificial Intelligence; Autoinducer-2; Microbiome–pathogen interactions; Multi-omics integration; Quorum quenching; Quorum-sensing; Systems microbiology; Translational opportunities
    DOI:  https://doi.org/10.1007/s00203-026-05085-0
  23. Antibiotics (Basel). 2026 Jun 26. pii: 638. [Epub ahead of print]15(7):
      The rapid rise of antimicrobial resistance (AMR) has created an urgent need for innovative therapeutic strategies beyond conventional antibiotics. Smart nano-antibiotics have emerged as advanced antimicrobial systems capable of improving drug delivery, enhancing pathogen targeting, overcoming biofilm-associated resistance, and reducing systemic toxicity. This review discusses recent progress in stimuli-responsive nanoplatforms, including pH-responsive, enzyme-responsive, temperature-sensitive, and redox-activated systems for precision antimicrobial therapy. The role of artificial intelligence in nanomaterial design, toxicity prediction, drug release optimization, and personalized treatment development is also critically examined. Furthermore, the review highlights targeted antimicrobial delivery, multifunctional nano-drug combination systems, biosensor integration, and autonomous AI-driven therapeutic platforms for combating multidrug-resistant infections. Current challenges related to toxicity, regulatory limitations, scalability, and AI data reliability are discussed alongside emerging clinical and industrial developments. Smart nano-antibiotics represent a promising next-generation approach for improving precision antimicrobial therapy and addressing the growing global burden of antimicrobial resistance.
    Keywords:  antimicrobial resistance; artificial intelligence; smart nano-antibiotics; stimuli-responsive nanocarriers; targeted drug delivery
    DOI:  https://doi.org/10.3390/antibiotics15070638
  24. Microbiol Resour Announc. 2026 Jul 27. e0060626
      Here, we describe the genomes of six Enterobacter bacteriophages (phages) of the genus Karamvirus. The range of genome length, GC content, and number of predicted protein-coding sequences were, respectively, 171,900-175,675 bp, 39.54-39.82%, and 298-316. Genomic analysis indicates that these phages have a lytic lifestyle and are suitable for therapeutic use.
    Keywords:  Enterobacter cloacae; Karamvirus; drug resistance; phage therapy; phages; virulent phages; whole genomes
    DOI:  https://doi.org/10.1128/mra.00606-26
  25. Pharmaceutics. 2026 Jun 25. pii: 776. [Epub ahead of print]18(7):
      Diabetic foot ulcers (DFUs) are among the most severe complications affecting diabetic patients, and dressing therapy is one of the standard treatments for DFUs. However, traditional dressings are inadequate for addressing the complex microenvironment of DFUs. Consequently, advanced natural polymer-based dressings have attracted extensive research attention in diabetic foot care due to their biocompatibility, low immunogenicity, and biodegradability. These natural polymer materials include collagen, gelatin, chitosan (CS), hyaluronic acid (HA), alginate, and cellulose. This review systematically analyzes the pathophysiological mechanisms underlying the difficult healing of DFUs and the advantages of natural polymer-based dressings in diabetic wound healing, highlights preclinical studies, and synthesizes evidence from clinical research. Moreover, we pinpoint the challenges associated with these dressings and propose future directions for the improvement of diabetic wound care.
    Keywords:  diabetes; dressing; natural polymer; wound healing
    DOI:  https://doi.org/10.3390/pharmaceutics18070776
  26. bioRxiv. 2026 Jul 17. pii: 2026.07.16.738945. [Epub ahead of print]
      Cystic fibrosis (CF) is a multisystem disease characterized by the accumulation of mucus in the airways that promotes pathogen colonization, leading to respiratory exacerbations, lung failure, and death. Culture-independent approaches have revealed that the CF airway harbors a complex microbiota, including opportunistic pathogens and bacteria that colonize the oropharynx. Here, we reanalyzed 5,260 16S rRNA gene microbiota datasets to infer ecological associations between members of the CF microbiota. We determined that pathogens are more likely to proliferate and dominate when present, while oropharyngeal bacteria are more likely to form persistent communities. Further, we found higher diversity and increasing numbers of inferred interactions were positively associated with lung function. In contrast, pathogens were negatively associated both with each other and with oropharyngeal bacteria, suggesting that they may disrupt the microbiota. To validate these predictions, we cultured 1,597 bacterial isolates from 96 people with CF and performed 12,542 coculture assays against eight representative CF pathogenic and oropharyngeal bacteria. 23% of these interactions resulted in growth inhibition. While Pseudomonas isolates were, on average, the most inhibitory, we observed variable activity among isolates. We then confirmed that Pseudomonas aeruginosa isolates, even those from the same donor and timepoint, exhibited significant differences in their metabolome and bioactivity profiles that correlated with acquisition of mutations. Together, our results suggest that pathogens may disrupt the CF microbiota and bloom in part through differential metabolite production. Furthermore, these data highlight that characterizing multiple isolates is necessary to capture the full landscape of chemically mediated interactions within microbial communities.
    Importance: The cystic fibrosis (CF) airway harbors a complex microbiota, including oropharyngeal bacteria and opportunistic pathogens that establish chronic infections and cause lung failure. We confirmed that microbiota diversity is correlated with health and that a pathogen-dominated microbiota is associated with reduced lung function. We then inferred microbial interactions, which suggested that pathogens are able to disrupt the microbiota. To validate these predictions, we cultured bacterial isolates from people with CF and performed thousands of coculture assays, finding that approximately one-quarter of interactions resulted in growth inhibition. Pseudomonas broadly inhibited other members of the CF airway microbiota. However, we observed marked variability in bioactivity and metabolite profiles of Pseudomonas aeruginosa isolates, even from the same donor at the same time. Our results suggest that pathogens disrupt the CF microbiota, possibly through bioactive metabolite production, and that characterizing multiple isolates is necessary to capture the complete picture of interactions in these communities.
    DOI:  https://doi.org/10.64898/2026.07.16.738945
  27. Pathogens. 2026 Jul 07. pii: 711. [Epub ahead of print]15(7):
      Foodborne pathogens remain a major public health challenge, particularly in the context of antimicrobial resistance and persistent contamination across animal, food-processing, and retail environments. This review examines bacteriophages as precision antimicrobials for controlling major foodborne bacteria, including Salmonella, Campylobacter, Shiga toxin-producing Escherichia coli (STEC), Listeria monocytogenes, and Vibrio spp., and summarizes the biological basis of phage-mediated control: strictly lytic life cycles, receptor-specific adsorption, direct bacterial killing, biofilm disruption, and resistance-associated fitness trade-offs. It further discusses pre-harvest, post-harvest, and processing-environment applications, with emphasis on matrix-dependent efficacy, delivery strategies, commercial products, and regulatory status. While bacteriophages offer high specificity and may help preserve the native microbiome, their integration into multi-hurdle food-safety systems require careful validation because their performance is influenced by narrow host ranges, bacterial resistance, food-matrix effects, formulation constraints, and regulatory complexity and scale-up challenges. Broader implementation will require rationally designed phage-cocktails, thorough genomic safety screening, matrix-specific validation studies, scalable manufacturing processes, and continuous monitoring for post-application resistance. Overall, bacteriophages should be viewed as promising but context-dependent adjuncts to validated food-safety and One Health frameworks, rather than stand-alone solution for reducing foodborne pathogen burdens.
    Keywords:  Campylobacter; Listeria monocytogenes; One Health; Salmonella; Shiga toxin-producing Escherichia coli; antimicrobial resistance; bacteriophages; biofilms; food safety; foodborne pathogens; phage biocontrol
    DOI:  https://doi.org/10.3390/pathogens15070711
  28. Clin Microbiol Infect. 2026 Jul 28. pii: S1198-743X(26)00399-X. [Epub ahead of print]
       BACKGROUND: Antimicrobial resistance (AMR) continues to threaten modern infectious diseases practice. Antimicrobial stewardship programs (ASPs) remain central to optimizing antimicrobial use, yet stewardship has become increasingly challenging because of rising clinical complexity, expanding data sources, and persistent workforce and analytic constraints. Artificial intelligence (AI) may strengthen stewardship by integrating clinical, microbiologic, and contextual data to support more timely and individualized decision-making.
    OBJECTIVES: To review current applications of AI in antimicrobial stewardship, with emphasis on resistance prediction and risk stratification, empiric therapy selection, diagnostic stewardship, antimicrobial optimization, and implementation challenges in clinical practice.
    SOURCES: Relevant studies evaluating AI and machine learning approaches for AMR prediction, diagnostic stewardship, antimicrobial optimization, and clinical implementation were reviewed.
    CONTENT: AI-based models have been developed to predict AMR and identify patients at risk for multidrug-resistant infections using electronic health record data. These approaches may support empiric therapy selection and patient-level risk stratification, although important methodological limitations remain, including heterogeneous prediction targets, data leakage, and limited external validation. AI applications also extend to diagnostic stewardship, including optimization of blood culture use, rationalization of molecular diagnostics, and support for interpretation of microbiologic results. In the therapeutic phase, AI may support de-escalation, intravenous-to-oral conversion, duration-of-therapy reassessment, and prioritization of stewardship review, aligning clinical decisions with antimicrobial stewardship goals. However, successful implementation depends not only on model performance but also on effective integration into clinical workflows, interpretability, governance, and clinician uptake.
    IMPLICATIONS: AI has the potential to enhance antimicrobial stewardship by enabling more precise, scalable, and workflow-integrated decision support. Future work should prioritize prospective and multicenter evaluation, careful implementation in routine care, and governance frameworks that address safety, transparency, equity, and clinician oversight. AI should be viewed as a tool to augment ASP expertise rather than replace clinical judgment.
    Keywords:  Antimicrobial resistance; Antimicrobial stewardship; Artificial intelligence; Clinical implementation; Diagnostic stewardship; Electronic health records
    DOI:  https://doi.org/10.1016/j.cmi.2026.07.032
  29. Microorganisms. 2026 Jul 03. pii: 1471. [Epub ahead of print]14(7):
      Stenotrophomonas maltophilia is an emerging multidrug-resistant opportunistic pathogen in intensive care units (ICUs) and cystic fibrosis (CF), where biofilm formation may favor persistence, device-associated colonization/infection, and clonal dissemination. This study compared biofilm formation, clonal relatedness, biofilm phenotypes, and motility in 37 ICU-associated and 42 CF-associated S. maltophilia isolates. Biofilm formation on polystyrene was quantified by crystal violet assay and expressed both as absolute biomass and as a growth-normalized Biofilm Index, calculated to account for differences in planktonic growth. Genetic diversity was assessed by pulsed-field gel electrophoresis, while swimming and twitching motility were evaluated using agar-based assays. ICU isolates showed a higher prevalence of biofilm formation, greater biofilm biomass, and higher growth-normalized Biofilm Index values than CF isolates. They also displayed lower genetic diversity and more frequent cross-transmission, supporting the circulation of selected hospital-associated lineages. Conversely, CF isolates showed greater heterogeneity and a more complex biofilm pattern, consistent with adaptation to a distinct chronic airway environment. Motility was not associated with biofilm formation, suggesting that the enhanced biofilm phenotype of ICU isolates is not explained by swimming or twitching alone. Overall, these findings support a setting-specific model in which enhanced biofilm-forming capacity may contribute to S. maltophilia ICU persistence and clonal dissemination, highlighting the need for targeted surveillance and careful device management.
    Keywords:  Stenotrophomonas maltophilia; biofilm formation; cross-transmission; cystic fibrosis; intensive care unit; molecular epidemiology
    DOI:  https://doi.org/10.3390/microorganisms14071471
  30. Microorganisms. 2026 Jul 14. pii: 1535. [Epub ahead of print]14(7):
       BACKGROUND: Oral squamous cell carcinoma (OSCC) has increasingly been associated with oral microbiota and chronic periodontal inflammation. While major periodontal pathogens have been extensively studied, the role of Capnocytophaga gingivalis (C. gingivalis) in oral carcinogenesis remains unclear. This study investigated the prevalence and quantified the presence of C. gingivalis in benign oral lesions, oral potentially malignant disorders (OPMDs), and OSCCs, as well as its association with carcinogenesis-related gene expression.
    METHODS: Ninety patients with periodontitis were included: 30 with benign lesions, 30 with OPMDs, and 30 with OSCCs. C. gingivalis quantification was performed using qPCR, while relative expression of VEGF, Cyclin D1, PIK3CA, DUSP16, mTOR, and MAPK14 was analyzed by RT-qPCR.
    RESULTS: C. gingivalis was detected in 2 benign lesions, 11 OPMDs, and 18 OSCC samples (p < 0.001). Overall bacterial burden was significantly higher in OPMD and OSCC groups compared to benign lesions (p = 0.001). Expression of PIK3CA and MAPK14 was significantly increased in the OPMD and OSCC groups. In OSCC samples, C. gingivalis abundance positively correlated with VEGF and Cyclin D1 expression.
    CONCLUSIONS: C. gingivalis showed progressively increased prevalence and abundance across examined lesions and was associated with altered expression of genes involved in carcinogenesis, supporting its potential role in OSCC progression.
    Keywords:  C. gingivalis; carcinogenesis; oral squamous cell carcinoma; periodontitis; qPCR
    DOI:  https://doi.org/10.3390/microorganisms14071535
  31. Nat Microbiol. 2026 Aug;11(8): 2112-2118
      Recurrent urinary tract infections are recalcitrant and difficult-to-treat bacterial infections that primarily affect women. Here we combine phage therapy with faecal microbiota transplantation to decolonize the urinary and intestinal reservoirs of patients with recurrent urinary tract infections. Three women received oral and intravesical phage therapy for 8 days, and two underwent subsequent faecal microbiota transplantation. Treatments were well tolerated, and although Escherichia coli was detected in follow-up samples, patients experienced none or fewer and less severe episodes of urinary tract infection 24 months post-treatment.
    DOI:  https://doi.org/10.1038/s41564-026-02409-0
  32. Life (Basel). 2026 Jul 13. pii: 1158. [Epub ahead of print]16(7):
      High-risk antibiotics remain indispensable in contemporary infectious diseases practice, yet they account for a disproportionate share of preventable toxicity, therapeutic drug monitoring complexity, and antimicrobial stewardship workload. Vancomycin, aminoglycosides, colistin, linezolid, daptomycin, selected beta-lactams, and amphotericin B are particularly challenging because clinically relevant exposure-toxicity relationships coexist with marked inter-patient variability and fragmented post-marketing safety surveillance. Artificial intelligence and real-world evidence are increasingly proposed as complementary approaches to address these limitations, although the evidence base remains heterogeneous and predominantly retrospective. This narrative review synthesises literature from PubMed/MEDLINE, Scopus, and Web of Science published between 2019 and April 2026, supplemented by citation chaining and regulatory pharmacovigilance resources, with studies prioritised by implementation maturity, external validation status, and stewardship relevance. Current evidence indicates that artificial intelligence may improve safety monitoring when embedded within clinically rich data environments: machine learning models show promising discrimination for nephrotoxicity and haematological toxicity in vancomycin, colistin, and linezolid therapy; natural language processing may enhance adverse drug event extraction from clinical text; and Bayesian, model-informed tools already demonstrate clinical utility in vancomycin and aminoglycoside dosing. However, prospective implementation data remain sparse, external validation is uncommon, and evidence that these tools improve real-world antibiotic safety outcomes, as opposed to predictive discrimination alone, remains limited. Artificial intelligence-enabled antibiotic safety monitoring is therefore transitioning from methodological promise towards conditional clinical utility rather than proven benefit. Near-term value is most likely to arise from integration with therapeutic drug monitoring, antimicrobial stewardship, and pharmacology-led clinical review rather than autonomous decision-making, with clinical pharmacologists and stewardship teams leading local implementation, validation, and governance of these tools.
    Keywords:  antimicrobial stewardship; artificial intelligence; drug safety; high-risk antibiotics; outpatient parenteral antimicrobial therapy; pharmacovigilance; real-world evidence; therapeutic drug monitoring
    DOI:  https://doi.org/10.3390/life16071158
  33. Nat Commun. 2026 Jul 30. pii: 7584. [Epub ahead of print]17(1):
      The clinical translation of phage therapy for multidrug-resistant infections is constrained by the lack of rapid, standardized therapeutic phage selection. Here, we introduce digital phage susceptibility testing (dPhaST), an automated droplet digital PCR workflow that quantifies phage-induced DNA release as a molecular signature of lysis. By targeting conserved 16S rRNA regions, dPhaST measures lytic activity across diverse bacterial pathogens within 3 h. Across 122 phage-host combinations involving 19 bacterial strains from six species, dPhaST shows 95.9% concordance with spot tests while resolving weak and heterogeneous lytic activities that are not readily distinguished phenotypically. It remains robust during the early infection window despite phage-encoded nuclease activity and tolerates phage cross-contamination better than spot tests. The method captures defense-mediated interactions involving CRISPR-Cas and Sir2-HerA systems. In this work, we show that automated digital quantification enables rapid and mechanistically informative profiling of early phage lytic efficacy across Gram-positive and Gram-negative pathogens.
    DOI:  https://doi.org/10.1038/s41467-026-75746-7
  34. Front Microbiol. 2026 ;17 1868543
      The escalating crisis of antimicrobial resistance (AMR) in poultry production necessitates innovative therapeutic approaches beyond conventional antibiotics. The outer membrane protein TolC, an essential component of the AcrAB-TolC multidrug efflux system, is consistently overexpressed in multidrug-resistant (MDR) avian pathogenic Escherichia coli, rendering it an attractive target for phage-based interventions. Here, we describe the development of a sequential positive-negative selection strategy designed specifically to isolate TolC-dependent bacteriophages from poultry farm environments without conventional liquid enrichment, thereby preserving natural phage diversity. Using this approach, we successfully isolated two novel TolC-dependent bacteriophages, PTolC-28 and PTolC-69, demonstrating their ability to combat MDR E. coli through two distinct mechanisms. Among the five MDR isolates susceptible to PTolC-28, one strain (GDW21C03) displayed a pronounced, strain-specific evolutionary trade-off upon developing resistance: despite maintaining an intact coding sequence, tolC mRNA expression decreased by over 60%, resulting in collateral resensitization to multiple antibiotic classes. The most pronounced reductions in minimum inhibitory concentrations (MICs) occurred for fluoroquinolones (~5.3-fold), tetracyclines, and aminoglycosides, all substrates of the TolC-dependent efflux system(s). Conversely, PTolC-69 did not induce antibiotic resistance reversal but exhibited robust phage-antibiotic synergy (PAS) with doxycycline (DOX) and florfenicol (FLR) (both substrates of the AcrAB-TolC efflux system), reducing the required antibiotic dosage by 8-fold in vitro. Importantly, this synergistic effect was confirmed in vivo using a chick infection model, where combined phage-antibiotic therapy decreased bacterial loads in lung and spleen tissues by nearly two orders of magnitude compared to either treatment alone. Collectively, these findings provide proof-of-concept evidence for an evolution-informed, dual-mechanism phage-based strategy to address antibiotic resistance in poultry production.
    Keywords:  TolC protein; avian pathogenic Escherichia coli; bacteriophage therapy; evolutionary trade-off; multidrug resistance; phage-antibiotic synergy; poultry production
    DOI:  https://doi.org/10.3389/fmicb.2026.1868543
  35. Microbiol Resour Announc. 2026 Jul 31. e0058625
      We report the genome of Luminis, a lytic bacteriophage isolated from wastewater using Pseudomonas aeruginosa mPAO1Δpf4Δpf6. Phage Luminis is a Yuavirus with 61,617 bp of circularly permuted dsDNA and 64.4% GC content. In addition to reference strains, Luminis plaques on two drug-resistant clinical isolates of P. aeruginosa.
    Keywords:  Pseudomonas aeruginosa; bacteriophage therapy; bacteriophages
    DOI:  https://doi.org/10.1128/mra.00586-25
  36. Lett Appl Microbiol. 2026 Jul 28. pii: ovag065. [Epub ahead of print]
      The increasing prevalence of multidrug-resistant Pseudomonas aeruginosa highlights the need for alternative therapeutic strategies. This study evaluated the potential of a commercial bacteriophage cocktail combined with antimicrobial agents and compared two practical methods for screening phage-antimicrobial synergy. A lytic bacteriophage isolated from the PYO phage cocktail was characterized by host range, size, pH and thermal stability, and lytic activity against the reference strain PAO1. Synergy was assessed with nine antimicrobial agents, including conventional antibiotics, efflux pump inhibitors, and essential oil compounds, using agar-based plaque assays and broth microdilution checkerboard assays. Plaque diameter and plaque number were evaluated at sub-MIC concentrations, whereas synergistic interactions were determined by the fractional inhibitory concentration index (FICI). Statistical significance was analyzed using one-way ANOVA followed by Dunnett's multiple comparison test, and the association between plaque parameters and FICI values was explored using Spearman's rank correlation. The isolated phage exhibited a burst size of approximately 259 PFU per infected cell and remained stable over a broad pH and temperature range, with significant reductions under highly acidic, highly alkaline, and high-temperature conditions. In agar-based assays, colistin, meropenem, and cinnamaldehyde significantly increased plaque diameter and/or plaque number (p < 0.05-0.001), depending on the bacterial strain tested. Checkerboard analysis identified the same four combinations as synergistic (FICI ≤ 0.5). Spearman's rank correlation indicated a relationship between plaque parameters and FICI values. Overall, both methods identified the same synergistic combinations, suggesting that agar-based plaque assays may serve as a practical preliminary screening tool for phage-antimicrobial combinations, although further validation is required.
    Keywords:   Pseudomonas aeruginosa ; Antibiotic; Bacteriophage; Efflux Pump Inhibitors; Essential Oil Components; Synergy
    DOI:  https://doi.org/10.1093/lambio/ovag065
  37. J Infect Public Health. 2026 Jul 22. pii: S1876-0341(26)00195-4. [Epub ahead of print]19(9): 103323
      Catheter-associated urinary tract infections (CAUTIs) remain a major contributor to healthcare-associated infections and antimicrobial resistance, compounded by diagnostic uncertainty that drives overtreatment of asymptomatic bacteriuria. Current passive prevention strategies have reached a plateau, leaving patients requiring prolonged catheterisation vulnerable to early biofilm formation. Historical irrigation approaches have largely failed because they target mature biofilms rather than the early formation phase (days 1-5). These approaches rely on manual techniques prone to contamination, poor standardisation, and high operational burden. Automated bladder irrigation is proposed to address these limitations through programmable early-phase intervention, closed-system sterility, and reduced dependence on healthcare worker handling. As a non-antibiotic approach, it may support infection prevention and antimicrobial stewardship by reducing CAUTI incidence and minimising diagnostic ambiguity that leads to inappropriate antimicrobial use. Therefore, effective CAUTI prevention requires a shift from passive catheter stewardship to active, biofilm-informed bladder management that addresses both infection control and antimicrobial resistance.
    Keywords:  Antimicrobial resistance; Antimicrobial stewardship; Biofilm; Bladder irrigation; Catheter-associated urinary tract infection; Healthcare-associated infections
    DOI:  https://doi.org/10.1016/j.jiph.2026.103323
  38. Front Endocrinol (Lausanne). 2026 ;17 1860867
       Background: Diabetic foot ulcers (DFUs) are a severe, costly complication of diabetes and a major public health challenge. Early multidisciplinary intervention is critical. This study investigated how pre-hospital practices affect clinical characteristics, metabolic profiles, and outcomes in DFU patients.
    Methods: A retrospective cohort study included DFU patients treated at a tertiary center (2021-2024). Patients were stratified into the timely medical care group (TMCG, ≤ 7 days) and the delayed medical care group (DMCG, 7-30 days) based on initial consultation timing. Comparative analysis evaluated metabolic parameters and lesion severity. Kaplan-Meier analysis was performed to assess healing outcomes, and multivariable Cox regression was used to identify predictors of DFU healing.
    Results: A total of 116 patients were enrolled in this study. A high proportion of patients in both the TMCG (n = 49) and DMCG (n = 67) had used Chinese herbal medicine or topical Western medications prior to admission. Compared to patients in the TMCG, those in the DMCG were associated with more severe Wagner grades (≥ 3: 38.8% vs. 18.4%, p = 0.02), hypoalbuminemia (< 35 g/L: 62.7% vs. 40.8%, p = 0.02), and higher rates of surgical intervention (14.9% vs. 4.1%, p = 0.02). Kaplan-Meier analysis revealed that the DMCG had a significantly higher risk of non-healing than the TMCG (p = 0.002). Multivariate Cox regression analysis identified delayed medical care (7-30 days) (HR = 1.62, 95% CI: 1.02-2.56, p = 0.04), and a higher Wagner grade (HR = 1.62, 95% CI: 1.19-2.22, p = 0.003) as independent predictors of impaired DFU healing.
    Conclusions: Inappropriate pre-hospital practices commonly delay definitive care and worsen outcomes. Early medical intervention (≤ 1 week) is positively associated with therapeutic outcomes and reduces the risk of complications.
    Keywords:  assessment; clinical characteristics; diabetic foot ulcers; outcomes; timely medical attention
    DOI:  https://doi.org/10.3389/fendo.2026.1860867
  39. BMC Microbiol. 2026 Jul 30. pii: 682. [Epub ahead of print]26(1):
      The clinical implementation of mycobacteriophages is hampered by the lack of standardized in vitro methods and inconsistent host range results, limiting reliable assessment of their therapeutic potential. Nontuberculous mycobacterial (NTM) infections are frequently difficult to treat, emphasizing the urgent need for alternative or adjunctive strategies to antibiotics. To facilitate reproducible translational research, a detailed and systematic understanding of in vitro assay conditions is essential. Here, we comprehensively evaluated commonly used liquid and solid media for their suitability in supporting growth of multiple NTM strains and subsequent phage application. We compared bacterial growth kinetics, aggregation tendencies, and the efficiency of phage-induced lysis, including plaque formation, across three liquid media and corresponding solid agars. Our results demonstrate that Middlebrook-based media and agar consistently support robust NTM growth, reduce bacterial clumping, and enable reproducible detection of phage activity, outperforming TSB-based alternatives despite higher cost and labor requirements. These findings provide a standardized framework for in vitro NTM cultivation and phage testing, which is critical for reliable evaluation of host range, infection dynamics, and the development of mycobacteriophage-based therapies.
    Keywords:  Cultivation comparison; Host range testing; Mycobacteriophages; Nontuberculous mycobacteria; Phage assay
    DOI:  https://doi.org/10.1186/s12866-026-05452-3
  40. Bull Exp Biol Med. 2026 Jul 28.
      Bacteria of the genus Moraxella are significant pathogens in both human clinical practice and veterinary medicine. A novel bacteriophage, designated vB_MboM_ZALNahr, was isolated from environmental sources (wastewater from the Moscow Region) and morphologically classified as a myovirus lytically active against Moraxella spp. The phage exhibits a broad spectrum of lytic activity, affecting 76% of the tested Moraxella isolates of various origins. Genome sequencing revealed integrase genes, indicating the temperate nature of the phage and limiting its therapeutic potential. Phylogenetic analysis demonstrated that the isolate is phylogenetically related to Bacillus phages. The obtained data indicate the potential of vB_MboM_ZALNahr as a specific diagnostic agent.
    Keywords:  Moraxella spp.; bacteriophage; genomic analysis; phage typing
    DOI:  https://doi.org/10.1007/s10517-026-06715-9
  41. Clin Case Rep. 2026 Aug;14(8): e73238
      Pan-drug resistant Klebsiella pneumoniae is a major therapeutic challenge, particularly when standard last-line agents are unavailable or contraindicated. We report a 45-year-old man with multifocal osteomyelitis and persistent purulent wound discharge despite broad-spectrum antibiotics, repeated debridement, and two sequential amputations. Wound culture grew K. pneumoniae resistant to all antibiotics tested in the locally available susceptibility panel. Initial treatment with colistin plus extended-infusion meropenem was discontinued because of acute kidney injury. Oral doxycycline 100 mg twice daily combined with rifampin 600 mg once daily was then initiated as salvage therapy, resulting in rapid resolution of purulent discharge and marked reduction in inflammatory markers. This case suggests that oral doxycycline plus rifampin may represent a low-cost and accessible salvage option for highly resistant K. pneumoniae infections when standard therapies are unavailable or not tolerated.
    Keywords:  Klebsiella pneumoniae; bacterial drug resistance; doxycycline; osteomyelitis; rifampin; wound infection
    DOI:  https://doi.org/10.1002/ccr3.73238
  42. Front Microbiol. 2026 ;17 1869585
      Acinetobacter baumannii-calcoaceticus complex (ABC complex) is recognized as one of the most critical multidrug drugs resistant (MDR) pathogens worldwide and remains a major cause of hospital-acquired infections, particularly in intensive care settings. Members of this complex are associated with ventilator-associated pneumonia, bloodstream infections, wound infections, urinary tract infections, and meningitis, often affecting critically ill and immunocompromised patients. Their clinical importance is primarily driven by their remarkable ability to acquire, accumulate, and maintain resistance determinants against multiple classes of antimicrobial agents. The ABC complex acquires resistance through diverse and coordinated mechanisms, including the production of β-lactamases, target-site alterations, efflux pump overexpression, reduced membrane permeability, horizontal gene transfer (HGT), and the mobilization of insertion sequences and other genetic elements that modulate intrinsic and acquired resistance genes. The rapid dissemination of these determinants has significantly limited therapeutic options and contributed to global outbreaks. Accurate identification of individual members within the complex is essential, as closely related species may differ in epidemiology and resistance profiles. A comprehensive understanding of molecular resistance mechanisms, reliable diagnostic approaches, and evolving treatment strategies, including combination therapies and novel agents, is crucial. This review summarizes current knowledge on resistance mechanisms, identification methods, and innovative therapeutic strategies, highlighting the need for integrated clinical and microbiological efforts to combat ABC complex infections.
    Keywords:  Acinetobacter baumannii–calcoaceticus complex; antimicrobial resistance mechanisms; combination therapy; efflux pumps; horizontal gene transfer; molecular diagnostics; multidrug resistance; β-lactamases
    DOI:  https://doi.org/10.3389/fmicb.2026.1869585
  43. J Clin Med. 2026 Jul 20. pii: 5689. [Epub ahead of print]15(14):
      Background/Objectives: Periodontitis is a chronic oral infection in which Porphyromonas gingivalis (Pg) acts as a keystone pathogen capable of systemic dissemination and immune evasion. A possible association between Pg and acute myocardial infarction (AMI) has been proposed; this systematic review is, to our knowledge, among the first to evaluate this association through a pathogen-specific synthesis integrating both microbial and serological evidence. Methods: Five electronic databases (PubMed, Scopus, Embase, Web of Science, Cochrane Library) were searched from inception to February 2025, with a supplementary top-up search performed in July 2026 that identified no additional eligible studies. Observational studies assessing Pg presence or anti-Pg antibody levels in participants with and without AMI were eligible. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). Findings were synthesised narratively due to substantial clinical and methodological heterogeneity. The protocol was registered in PROSPERO (CRD42025644043). Results: Twelve case-control studies (5147 participants; 2518 AMI cases, 2629 controls) were included. Six evaluated serum anti-Pg antibodies and six used direct microbial or molecular detection. Three studies in each category reported a significant Pg-AMI association; three in each category did not. NOS scores ranged from 6 to 9 (eight studies rated good quality; four fair quality). Heterogeneity in antigen selection, sampling site, immunoglobulin isotype, and confounder adjustment precluded meta-analysis. Conclusions: The available evidence suggests a possible but inconsistent association between Pg and AMI, insufficient to establish a causal relationship. Standardised detection protocols and prospective longitudinal studies with comprehensive confounder adjustment are needed. The detection of Pg in isolation is not currently validated for AMI risk stratification, and the available evidence does not establish a causal relationship between Pg and AMI.
    Keywords:  Porphyromonas gingivalis; cardiovascular diseases; myocardial infarction; periodontitis; systematic review; virulence
    DOI:  https://doi.org/10.3390/jcm15145689
  44. Int Wound J. 2026 Aug;23(8): e70997
      Despite strong evidence that nutrition is critical for wound healing, its integration into outpatient practice remains inconsistent. This study aimed to explore how nutrition is perceived, communicated, and experienced in outpatient wound care-encompassing healthcare professionals' clinical practice and professional reasoning, and patients' lived experiences. This multicentre qualitative study using Interpretive Description generated data through 156 h of field observations, five focus groups with nurses (n = 19), and interviews with patients with foot ulcers (n = 9) across six outpatient clinics in Denmark. Nutrition was acknowledged as fundamental to wound healing, yet communication remained brief, non-specific, and rarely actionable. Nurses adopted pragmatic, patient-adapted approaches shaped by unclear role responsibility, time constraints, and limited tools, resulting in opportunistic rather than systematic care. Patients had limited understanding of nutrition's role in wound healing, reflecting insufficient explanation rather than disengagement. Relational continuity and communication quality were determinants of whether nutrition became a meaningful component of care. Patients were willing to engage when advice was concrete and tailored to their everyday context. A persistent gap exists between the acknowledged importance of nutrition and its enactment in outpatient wound care, sustained by organisational, communicative, and role-related ambiguities, with implications for nursing education, interdisciplinary roles, and clinical pathways.
    Keywords:  foot ulcer; nutrition; outpatient practice; patient experience; qualitative research; wound care
    DOI:  https://doi.org/10.1111/iwj.70997
  45. Front Immunol. 2026 ;17 1852272
      Periodontitis is a chronic immunoinflammatory disease characterized by site-specific destruction of the tooth-supporting tissues and marked heterogeneity in disease susceptibility, progression, and response to therapy. While dysbiotic subgingival biofilms initiate disease, microbial burden alone cannot explain the persistence of inflammation or the limited predictability of regenerative outcomes. Increasing evidence implicates innate immune dysregulation, particularly Toll-like receptor (TLR) signaling, as a central determinant of periodontal disease behavior. This narrative review synthesizes current evidence on TLR signaling in periodontal tissues, emphasizing the concept that chronic periodontitis is sustained by biased downstream signaling integration rather than uniform receptor overactivation. We discuss how persistent dominance of pro-inflammatory, MyD88-dependent pathways, coupled with insufficient engagement of regulatory and resolution-associated programs, promotes inflammatory persistence, osteoimmune imbalance, and functional impairment of periodontal stromal and stem/progenitor cells. Cell-type-specific responses to TLR activation, genetic modulation of signaling thresholds, and reciprocal interactions between innate immunity and dysbiosis are examined as key contributors to disease heterogeneity. We further explore the implications of biased TLR signaling for periodontal regeneration, proposing that regenerative failure reflects an unfavorable inflammatory signaling milieu rather than depletion of regenerative cell populations. Finally, emerging experimental strategies for interrogating and modulating TLR signaling networks-including localized immune modulation and targeted protein degradation approaches-are discussed as mechanistic research tools rather than immediate therapeutic solutions. By reframing periodontitis as a disorder of maladaptive innate immune signaling integration, this review provides a unifying conceptual framework linking dysbiosis, host-response heterogeneity, and impaired regeneration, and defines priorities for future mechanistic and translational research.
    Keywords:  MyD88; innate immunity; mesenchymal stem cells; osteoimmunology; periodontal regeneration; signaling bias; toll-like receptors
    DOI:  https://doi.org/10.3389/fimmu.2026.1852272
  46. Front Microbiol. 2026 ;17 1859270
       Introduction: Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a major global health challenge, particularly due to the increasing emergence of multidrug-resistant strains and limited treatment options. Bacteriophages have gained attention as potential alternatives or adjuncts to conventional antibiotics owing to their host specificity and antibacterial efficacy.
    Methods: This study reports the isolation and detailed characterization of mycobacteriophage Kashi_RDG1 (KRDG1), isolated using Mycobacterium smegmatis mc2155. Genomic analysis, transmission electron microscopy, host range analysis, one-step growth assay, adsorption assay, multiplicity of infection (MOI) determination, and infection kinetics were performed to characterize the phage.
    Results: Genomic analysis identified KRDG1 as sub cluster K1 mycobacteriophage, with a genome size of 58,681 bp containing 95 predicted open reading frames (ORFs), of which 39 are functionally annotated. Transmission electron microscopy analysis confirmed its siphovirus-like morphology while host range analysis depicted its polyvalent activity against Mycobacterium fortuitum (opportunistic pathogen) and M. tuberculosis H37Ra (an attenuated Mtb strain) in addition to M. smegmatis. One-step growth analysis revealed latent period of 80 min and burst size of 100 phage/bacterial cell supporting its efficient infection dynamics. Notably, infection kinetics demonstrated strong host bacterial killing during the logarithmic phase.
    Discussion: While KRDG1 exhibits temperate characteristics, its close genomic similarity to previously engineered therapeutic phage (ZoeJ) highlights its potential for future genetic engineering and therapeutic exploration against pathogenic mycobacterial and non-mycobacterial infections.
    Keywords:  KRDG1; Mycobacterium tuberculosis; antibiotic resistance; cluster K1 mycobacteriophage; multiplicity of infection; phage therapy; temperate phage
    DOI:  https://doi.org/10.3389/fmicb.2026.1859270
  47. J Clin Med. 2026 Jul 14. pii: 5510. [Epub ahead of print]15(14):
      Background/Objectives: Metabolic syndrome (MetS), defined by abdominal obesity, dysglycemia, dyslipidemia, hypertension, and insulin resistance, markedly increases the risk of type 2 diabetes mellitus and cardiovascular disease. Affecting an estimated 25-30% of the global adult population, MetS represents a major and growing public health challenge. A growing body of evidence supports a significant bidirectional relationship between MetS and oral health, particularly periodontitis. The present study aimed to synthesize current evidence on the pathophysiological mechanisms, epidemiological associations, interventional outcomes, and clinical implications of the bidirectional relationship between metabolic syndrome (MetS) and periodontitis. Methods: A narrative review following the SANRA framework was performed. PubMed, Scopus, and Web of Science were searched for articles published in January 2021-March 2026 using MeSH and free-text terms including "metabolic syndrome", "periodontal disease", "insulin resistance", and "oral microbiota". Eligible studies included original research and systematic reviews in English with full-text availability; animal and in vitro studies were included if directly informative of mechanistic pathways. Results: A total of 64 references were selected for inclusion. Shared mechanisms include chronic systemic inflammation, insulin resistance, oxidative stress, adipokine imbalance, endothelial dysfunction, and oral-gut microbiome dysbiosis. Cross-sectional and longitudinal studies show that MetS components are independently associated with higher prevalence and severity of periodontitis; meta-analyses report pooled odds ratios of 1.7-1.9 compared with metabolically healthy controls. Non-surgical periodontal therapy produces modest but significant reductions in glycated hemoglobin (HbA1c) and systemic inflammatory markers. Sodium-glucose cotransporter-2 (SGLT2) inhibitors may alter oral microbiota composition and cause mucosal changes, while glucagon-like peptide-1 (GLP-1) receptor agonists may increase caries risk through gastrointestinal side effects and xerostomia; both drug classes warrant proactive dental monitoring. Conclusions: The bidirectional relationship between MetS and oral health supports integrated screening and interdisciplinary management. Routine periodontal assessment should be integrated into the metabolic risk management pathway, and dental professionals should screen patients with severe periodontitis for metabolic risk factors. The oral microbiome emerges as a promising target for future mechanistic research and therapeutic intervention. Recognition of oral health as an integral component of metabolic health may improve risk stratification, prevention, and long-term patient outcomes. Large-scale randomized controlled trials with standardized endpoints are needed to establish causal directionality and optimize combined therapeutic strategies.
    Keywords:  bidirectional relationship; cardiovascular disease; insulin resistance; interdisciplinary care; metabolic syndrome; oral microbiota; periodontal disease; periodontal therapy; systemic inflammation
    DOI:  https://doi.org/10.3390/jcm15145510
  48. Microorganisms. 2026 Jun 29. pii: 1420. [Epub ahead of print]14(7):
      Background: Burning mouth syndrome (BMS) is a chronic orofacial pain disorder characterized by persistent intraoral burning recurring daily for at least 2 h over more than 3 months, without explanatory mucosal or laboratory findings. It affects 1.7-7.7% of the population, predominantly perimenopausal and postmenopausal women, and conventional pharmacotherapy offers only partial relief. Aim: This narrative review examines the associative and mechanistic evidence linking the oral microbiome to BMS and evaluates the rationale for lactic acid bacteria (LAB) as a candidate therapeutic strategy. Methods: PubMed/MEDLINE, Scopus, and Web of Science were searched for English-language literature on BMS, the oral microbiome, and probiotics, supplemented by mechanistic data from related conditions. Results: BMS patients may exhibit a compositionally distinct salivary microbiome, with reduced alpha diversity in psychiatric-comorbid subsets, though findings are heterogeneous. LAB, particularly Lacticaseibacillus paracasei, show antimicrobial and immunomodulatory properties relevant to oral homeostasis, but direct clinical evidence in BMS remains scarce and largely preclinical. Conclusions: Current evidence is predominantly cross-sectional and associative; the oral dysbiosis-BMS link and the therapeutic potential of LAB should be regarded as hypothesis-generating, warranting biomarker-anchored, strain-specific randomized trials.
    Keywords:  burning mouth syndrome; dysbiosis; gut–brain axis; lactic acid bacteria; oral microbiome; orofacial pain; probiotics
    DOI:  https://doi.org/10.3390/microorganisms14071420
  49. Microorganisms. 2026 Jul 14. pii: 1534. [Epub ahead of print]14(7):
      Healthcare-associated infections represent a global public health challenge, primarily driven by biofilm-forming multidrug-resistant pathogens on medical device surfaces, leading to high morbidity, mortality, and healthcare costs. As antibiotic strategies fail due to antimicrobial resistance, this study investigates a primary-prevention nanotechnology strategy based on the photochemical functionalization of clinically relevant substrates (polyurethane venous catheters, cotton gauze, and glass-fiber HEPA filter membranes) with immobilized silver nanoparticles. While the photochemical deposition ensures a controlled silver release experimentally quantified here by ICP-MS (≈0.44 ppm·day-1) within safety thresholds, the core value of this functionalization lies in its broad-spectrum and long-term efficacy. Agar diffusion assays performed against a panel of 10 multidrug-resistant clinical isolates, including pathogens such as Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus epidermidis, Candida parapsilosis, and Aspergillus sydowii, demonstrated antimicrobial activity over 15 days across all substrates. Biofilm quantification by Crystal Violet Assay revealed inhibition exceeding 97% for bacterial strains and 96% for fungal species at day 15. By preventing both bacterial and fungal colonization on diverse materials, these results validate silver-functionalized surfaces as an effective and bio sustainable approach to combat healthcare-associated infections and antimicrobial resistance. This strategy holds significant promise for translation into clinical settings, hospital air filtration systems, and wound care applications, aligning with Antimicrobial Stewardship and One Health principles.
    Keywords:  HEPA filters; antimicrobial resistance; biofilm; catheters; healthcare-associated infections; medical devices; multidrug resistant pathogens; nanomedicine; photoreduction; silver nanoparticles
    DOI:  https://doi.org/10.3390/microorganisms14071534
  50. Microbiology (Reading). 2026 Jul;172(7):
      Pseudomonas aeruginosa and Aspergillus fumigatus represent the dominant bacterial and fungal pathogens in the lungs of adults with cystic fibrosis. Understanding how these species interact with each other and the host may provide insight into pathology and microbial succession in the lung. The ex vivo pig lung model is suitable for studying host responses to pathogens in an ethical and cost-effective manner due to its rich cell complexity and anatomical and immunological similarities to humans. Metagenomic analysis demonstrated that A. fumigatus promoted the proliferation of Pseudomonadota and P. aeruginosa in coinfected explants. Proteomic analysis of coinfected alveolar lung explants identified reduced virulence of A. fumigatus in competition with P. aeruginosa with reductions in abundance of dipeptidyl-peptidase 5 (-10.30-fold) and thioredoxin reductase gliT (-11.72-fold) and a reduction in amide biosynthetic processes. P. aeruginosa flourished in coinfected tissue and increased protein translation and amino acid biosynthesis and cellular nitrogen utilization. Examination of changes in the porcine proteome indicated specific nutritional utilization with A. fumigatus inducing greater complement activation and utilization of amino acids, while P. aeruginosa infection induced greater natural killer cell toxicity and potential butanoate metabolism from the host. Increased abundance of proteins associated with inflammation and immune activation was observed in coinfected samples relative to the mono-infected tissues. Coinfection also resulted in the reduction in abundance of ferritin and lactotransferrin, which may indicate elevated bioavailability of iron that could facilitate P. aeruginosa virulence.
    Keywords:  Aspergillus; Pseudomonas; co-infection; ex vivo; infection; porcine; proteomics
    DOI:  https://doi.org/10.1099/mic.0.001745
  51. Microorganisms. 2026 Jun 30. pii: 1447. [Epub ahead of print]14(7):
      The TM7x strain is a genetic variant of the bacterium Nanosynbacter lyticus, which belongs to the Saccharibacteria phylum within the Candidate Phyla Radiation (CPR) or Patescibacteria group. Its biology differs significantly from that of other bacterial phyla, and its ecological role in the oral cavity remains largely undefined. Through a organyzed and comprehensive literature review, we aim to define the role this bacterium plays within the oral ecosystem. We identified relevant studies from primary sources, including scientific articles from preclinical and clinical studies obtained from three digital databases. The bacterial strain TM7x is an obligate epibiont that exhibits autonomous energy metabolism and utilizes a type IV pili system to adhere to its direct host, Schaalia odontolytica. It interacts with its host in two stages: initially as an epipatobiont and subsequently as an episymbiont. TM7x plays a complex ecological role by modulating the host's metabolism and structure toward a less virulent phenotype resistant to phage attack, while also influencing the human host through immunomodulation and tissue protection. This organism has transitioned from being considered 'biological dark matter' to a key model for understanding coevolution within the human microbiome. Its ability to protect the host from phages, induce protective biofilms, and suppress destructive inflammatory responses suggests its potential role as a speculative modulator of human oral microbiome homeostasis, although direct clinical confirmation in human subjects is still lacking.
    Keywords:  Nanosymbacter lyticus; Saccharibacteria; TM7x; ecology; oral microbiome
    DOI:  https://doi.org/10.3390/microorganisms14071447
  52. Int Dent J. 2026 Jul 28. pii: S0020-6539(26)00355-2. [Epub ahead of print]76(5): 109762
       INTRODUCTION AND AIMS: The tongue dorsum represents a structurally complex oral biofilm niche that has traditionally been regarded as indicative of systemic health. Recent advances in oral microbiome research and multi-omics technologies facilitate the systematic evaluation of the association between tongue coating biofilm signals and gastrointestinal disease states. However, it remains unclear whether these tongue-derived signals indicate systemic gastrointestinal pathology or merely reflect localised oral ecological disturbances. This review synthesises current evidence on tongue-derived microbial and multi-omics signatures across inflammatory, precancerous, and malignant gastrointestinal conditions, and evaluates their ecological, biological, and clinical significance.
    METHODS: A scoping review was conducted in accordance with PRISMA-ScR guidelines. Five electronic databases were searched (2010-2025) for human studies analysing tongue-coating samples using microbiome or multi-omics approaches.
    RESULTS: A total of twenty-five cross-sectional studies involving more than 4500 participants, primarily from East Asian populations, were included. Three recurrent patterns were identified: (1) stage-associated microbial restructuring, which involved mild non-specific alterations in inflammatory states, structured dysbiosis in precancerous conditions, and more consistent ecological configurations in malignancy; (2) convergence of functional multi-omics signals on lipid metabolism pathways across independent cohorts; and (3) significant modification of microbial and functional profiles by tongue coating phenotype, including colour, thickness and classification system.
    CONCLUSIONS: Tongue-derived microbial and multi-omics signatures demonstrate reproducible cross-sectional associations with gastrointestinal diseases, exhibiting functional convergence across multiple omics layers. However, the reliance on cross-sectional study designs, absence of external validation and insufficient adjustment for confounding variables currently limit their clinical application as diagnostic biomarkers.
    CLINICAL RELEVANCE: Tongue examination is clinically useful for assessing oral biofilm burden, mucosal pathology and oral hygiene in dental practice. It should not be used to diagnose gastrointestinal disease until validated by longitudinal, confounder-controlled studies.
    Keywords:  Biomarkers; Gastrointestinal diseases; Healthcare access; Oral-gut axis; Precancerous lesions; Tongue microbiome
    DOI:  https://doi.org/10.1016/j.identj.2026.109762
  53. iScience. 2026 Aug 21. 29(8): 116797
      A mechanistic understanding of how genetic variants alter drug-receptor binding is central to precision medicine, drug response prediction, and drug development. Yet, experimental mutation-drug profiling remains slow and expensive, while existing computational approaches often trade accuracy for scalability. We developed BoltzOmics, an interactive, open-source platform that integrates Boltz-2, a deep learning model for biomolecular structure prediction, to rapidly assess mutation effects on drug binding. Starting from amino acid sequences, the workflow queries databases for genetic variants, generates wild-type and mutant protein structures, and screens multiple drugs across variants to predict binding affinity changes. We evaluated BoltzOmics across four targets: hERG, NaV1.5, HER2, and CYP3A4. Predictions achieved Pearson correlations with experimental drug IC50 data up to 0.76 for wild-type proteins and 0.60 for mutants. By enabling scalable, high-throughput assessment of drug-variant interactions, BoltzOmics establishes a practical AI-driven framework for accelerating computational drug discovery and advancing precision medicine research.
    Keywords:  computational drug discovery; deep learning; drug binding; genetic variants; precision medicine; protein structure prediction
    DOI:  https://doi.org/10.1016/j.isci.2026.116797
  54. Microbiol Res. 2026 Jul 27. pii: S0944-5013(26)00214-4. [Epub ahead of print]312 128650
      This review provides an integrative analysis of the current knowledge on Klebsiella pneumoniae quorum sensing (QS) network. Although it is widely recognised as a high-priority ESKAPE pathogen, the regulatory networks coordinating its virulence and persistence remain insufficiently understood. Here, we examine QS as regulatory framework linking pathogenicity, including multidrug resistance. We first synthesise the major stages of infection, virulence factors related, and molecular basis of antibiotic resistance and immune evasion. We then focus on the four main QS systems described in K. pneumoniae (AHL-SdiA, AI-2-Lsr complex, QseBC-AI-3, and indole-CpxAR), highlighting their individual roles and potential interactions in controlling virulence-associated phenotypes. Overall, while direct experimental validation remains limited, the available evidence suggests that QS in K. pneumoniae likely functions as a complex and interconnected regulatory network rather than as independent signalling pathways. Understanding how these systems coordinate bacterial behaviour is essential for bridging the gap between genomic data and phenotypic expression. In this context, targeting QS emerges as a promising anti-virulence strategy aimed at disarming the pathogen, potentially reducing selective pressure for resistance and contributing to the development of alternative therapeutic approaches.
    Keywords:  AI-2; AI-3; Indole; Klebsiella pneumoniae; Quorum sensing; SdiA; Virulence
    DOI:  https://doi.org/10.1016/j.micres.2026.128650
  55. Antibiotics (Basel). 2026 Jul 22. pii: 710. [Epub ahead of print]15(7):
      Severe bacterial keratitis and endophthalmitis are leading causes of corneal scarring, enucleation, and permanent vision loss, and are increasingly complicated by multidrug-resistant Gram-positive ocular pathogens. In the United States, according to the ARMOR surveillance program (2009-2020), methicillin resistance reached 45.9% of intraocular Staphylococcus aureus and 47.9% of coagulase-negative staphylococci (CoNS), with multidrug resistance exceeding 70% among methicillin-resistant intraocular isolates. While new antibiotics have been approved for systemic infections, vancomycin remains the standard of care for severe Gram-positive ocular infections. However, its ophthalmic use is constrained by limited ocular surface tolerability, physical incompatibility with intravitreal ceftazidime, and an association with hemorrhagic occlusive retinal vasculitis. To address this gap and further stimulate the development of next-generation targeted therapies in ophthalmology, this review focuses on current recommendations and new vancomycin alternative treatments for Gram-positive ocular infections in the antibiotic resistance era. This review details the current antimicrobial recommendations for the most frequent ocular infections, followed by the epidemiology and molecular mechanisms of resistance in S. aureus, CoNS, and S. pneumoniae. Finally, this review discusses new drugs that represent promising alternatives to vancomycin in ophthalmology.
    Keywords:  Gram-positive ocular infection; MRSA; antimicrobial resistance; antimicrobial stewardship; endophthalmitis; ocular pharmacokinetics; vancomycin-alternative therapy
    DOI:  https://doi.org/10.3390/antibiotics15070710
  56. Arq Gastroenterol. 2026 ;pii: S0004-28032026000105006. [Epub ahead of print]63 e25141
       BACKGROUND: Acute-on-chronic liver failure (ACLF) affects approximately one-third of patients hospitalized for acute decompensation of cirrhosis. These patients exhibit an extremely high degree of systemic inflammation, and infections as well as severe alcohol-related hepatitis are the most common precipitating factors of ACLF.
    OBJECTIVE: This paper aims to discuss the most relevant aspects of ACLF emphasizing the role of gut dysbiosis.
    METHODS: This review includes clinical and epidemiological studies, meta-analyses, and other articles published in English and indexed in the following databases: PubMed, Scopus, and Embase. Only full-text articles were selected.
    RESULTS: ACLF is the most severe complication in patients with cirrhosis and is associated with high mortality rates. Bacterial translocation is considered responsible for the systemic inflammation leading to acute decompensation of cirrhosis when other precipitating events are not identified. Different microbiome profiles may influence the incidence of decompensation and thus the clinical course of the disease. Dysbiosis causes intestinal inflammation, which contributes to gut barrier dysfunction and pathological bacterial translocation, the main triggering factor of the cascade leading to acute decompensation of cirrhosis and multiple organ failure. Since dysbiosis plays a central role in the pathophysiology of acute decompensation of cirrhosis and ACLF, it is expected that treatments targeting the microbiome could modify the course of the disease. Despite current limitations, the role of probiotics, prebiotics, postbiotics, rifaximin, bacteriophages, and fecal microbiota transplantation is discussed in the present review.
    CONCLUSION: ACLF is a highly significant complication of liver disease. Dysbiosis and the gut-liver axis play key roles in its pathophysiology. This knowledge supports the idea that manipulation of the microbiome may be a potential therapeutic strategy.
    DOI:  https://doi.org/10.1590/S0004-2803.24612025-141
  57. Front Cell Infect Microbiol. 2026 ;16 1842791
      Porphyrins are versatile biomolecules central to the synthesis of many essential molecules across all domains of life. Their ability to absorb light, accept electrons and facilitate redox reactions underpins diverse biological roles. Importantly, porphyrin properties can be easily tailored through substitutions of side chains and chelated metals. This adaptability has enabled porphyrins to play critical roles in bacterial environmental adaptations, most notably in enhancing competitive advantage and virulence. The association between porphyrin adaptations and virulence in pathogenic bacteria presents a unique opportunity for the development of next-generation antibacterial strategies and therapeutics. By focusing on virulence and virulence-related systems, these innovative strategies aim to address antimicrobial resistance by reducing the selective pressures that drive its emergence, promote evolutionary pathways that favor non-pathogenic adaptations and help to restore the balance of commensal microbiota. This review highlights the recent advances in porphyrin and porphyrin-related antibiotic developments, with emphasis on approaches targeting virulence versus bacterial survival. We further discuss emerging virulence-targeted therapeutics, including artificial intelligence and machine learning for novel target and lead discovery.
    Keywords:  antimicrobial development; antimicrobial resistance; bacterial virulence; heme biology; host-pathogen interactions; porphyrin biology
    DOI:  https://doi.org/10.3389/fcimb.2026.1842791
  58. Nurs Rep. 2026 Jul 14. pii: 242. [Epub ahead of print]16(7):
      Background: Bronchiectasis is a chronic respiratory condition characterised by irreversible airway dilation and recurrent infections, resulting in significant symptom burden and frequent healthcare utilisation. Although nurses are central to chronic respiratory disease management, their specific roles and responsibilities in outpatient bronchiectasis care remain poorly defined. Understanding these roles is imperative to support workforce planning, optimise multi-disciplinary collaboration, and improve patient outcomes. Aim: This scoping review aimed to map and synthesise existing evidence on the roles and responsibilities of nurses involved in the outpatient management of adults with non-cystic fibrosis bronchiectasis. Methods: A scoping review was conducted. Six databases were systematically searched (MEDLINE, CINAHL Complete, Central, Web of Science, and ProQuest Dissertations and Theses Citation Index). Records describing nursing roles, responsibilities, or models of care within outpatient bronchiectasis settings were included (any design). Data was analysed descriptively and thematically. Results: Five studies and two international clinical practice guidelines published between 2002 and 2025 were included. Nurses were shown to play roles across five key domains: 1. clinical assessment and monitoring, 2. self-management support and patient education, 3. care co-ordination and multi-disciplinary collaboration, 4. patient advocacy and communication, and 5. leadership and service development. Evidence on measurable outcomes and standardised role definitions remains limited. Conclusions: This review mapped five domains within which nurses may contribute to outpatient bronchiectasis care; however, most identified roles and responsibilities were derived from multi-disciplinary recommendations rather than explicit descriptions of nursing practice. Further research is required to better define nursing roles and responsibilities and evaluate nurse-led models of care in bronchiectasis outpatient care settings.
    Keywords:  bronchiectasis; health workforce; nurses; outpatient; respiratory tract diseases
    DOI:  https://doi.org/10.3390/nursrep16070242
  59. Diagn Microbiol Infect Dis. 2026 Jul 25. pii: S0732-8893(26)00327-5. [Epub ahead of print]116(3): 117577
      Chronic Pseudomonas aeruginosa infections in cystic fibrosis are characterized by biofilm formation, which substantially alters antimicrobial susceptibility profiles. In this study, planktonic minimum inhibitory concentration (MIC) and minimum biofilm eradication concentration (MBEC) values were compared for P. aeruginosa isolates obtained exclusively from patients with cystic fibrosis using a peg-based biofilm model. All tested antimicrobials showed significantly reduced susceptibility under biofilm conditions compared with planktonic conditions (p < 0.0001), and no isolate exhibited an MBEC value lower than its corresponding MIC. While ciprofloxacin, amikacin, tobramycin, and azithromycin retained relatively more preserved activity in the biofilm state, beta-lactams, levofloxacin, and colistin showed pronounced loss of efficacy. These findings highlight the biological and clinical relevance of biofilm-associated antimicrobial tolerance in cystic fibrosis and support the potential role of biofilm-based susceptibility testing as a complementary tool to conventional MIC testing in selected clinical contexts.
    Keywords:  Antimicrobial susceptibility testing; Biofilm; Cystic fibrosis; Minimum biofilm eradication concentration; Minimum inhibitory concentration; Pseudomonas aeruginosa
    DOI:  https://doi.org/10.1016/j.diagmicrobio.2026.117577
  60. Front Cell Infect Microbiol. 2026 ;16 1873050
      Dry eye disease is a multifactorial, heterogeneous ocular surface disorder characterized primarily by an imbalance in tear film homeostasis. The traditional classification into "aqueous deficiency" and "evaporative" types fails to fully account for the differences in its inflammatory biology, clinical manifestations, and treatment responses. In recent years, the gut microbiota has been implicated in influencing ocular surface homeostasis through immune-inflammatory, metabolic-barrier, and neuroimmune pathways; however, the magnitude of its effects and their biological significance may vary depending on the specific phenotype of dry eye disease (DED). This article reviews the current evidence regarding the gut-ocular surface axis in dry eye disease from a phenotype-specific perspective, categorizing it into direct clinical evidence, animal and mechanistic evidence, indirect and inferential evidence, and hypothesis-generating evidence based on the source and directness of the evidence. The existing evidence is primarily focused on Sjögren syndrome-associated and other immune-mediated forms of dry eye disease. Clinical microbiome studies, germ-free animal models, antibiotic-induced dysbiosis models, and patient-derived microbiota transplantation experiments all suggest that gut microbiota dysbiosis may contribute to systemic immune remodeling and lacrimal-ocular surface inflammatory responses. In contrast, for dry eye syndromes dominated by meibomian gland dysfunction or evaporative dry eye, as well as non-Sjögren aqueous-deficient dry eye, current evidence is primarily supported indirectly by studies on metabolic susceptibility, local microbiome, and animal mechanisms; whereas postoperative, environment-related, and symptom-sign incongruence types of dry eye are more often characterized by early clues or research hypotheses related to host inflammatory thresholds, ocular surface repair capacity, and neuroimmune regulation. Although microbiome-targeted interventions (including probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation) have demonstrated some translational potential, they remain limited by small sample sizes, high heterogeneity in study designs, short follow-up periods, and a lack of validation through phenotypic stratification. Future research should shift from general descriptions of microbial differences to stratified cohorts, causal validation, functional multi-omics analysis, and mechanism-driven intervention trials to clarify the true role of the gut microbiota in different DED phenotypes and to advance the development of precision adjunctive treatment strategies.
    Keywords:  disease heterogeneity; dry eye disease; gut microbiota; gut-eye axis; microbiome intervention; ocular surface homeostasis
    DOI:  https://doi.org/10.3389/fcimb.2026.1873050
  61. Microorganisms. 2026 Jul 14. pii: 1536. [Epub ahead of print]14(7):
      The vaginal microbiome is often interpreted through static taxonomic patterns. Yet microbial composition alone does not explain why some communities resist perturbation, recover after disruption, or transition toward dysbiosis. This narrative review synthesizes evidence that vaginal microbiome stability is shaped by endocrine phase, epithelial substrate availability, microbial functional capacity, mucosal tone and candidate host modifiers. High-estrogen states, particularly pregnancy, are associated with epithelial maturation, glycogen accumulation, low vaginal pH, and Lactobacillus-dominant communities, whereas postpartum, lactational, menopausal, and other hypoestrogenic states are associated with reduced epithelial support and increased vulnerability to diverse anaerobe-rich configurations. We review the linking of the estrogen-glycogen-Lactobacillus axis, focusing on microbial functions involved in glycogen degradation, lactate production and biofilm persistence, and host pathways that may modify mucosal responsiveness. Direct human genotype-to-vaginal-microbiome stability evidence remains limited; therefore, host genetic features are treated as candidate modifiers rather than validated clinical predictors. We propose a conceptual multi-omic hierarchy for organizing endocrine, epithelial, microbial, immune, temporal, and candidate host-modifier domains relevant to vaginal microbiome resilience. This framework is hypothesis-generating and requires longitudinal, phase-resolved human validation before quantitative prediction or clinical application.
    Keywords:  Gardnerella diversity; Lactobacillus dominance; bacterial vaginosis; estrogen–glycogen axis; genetic–hormonal interface; host–microbe interactions; vaginal microbiome
    DOI:  https://doi.org/10.3390/microorganisms14071536
  62. Dent J (Basel). 2026 Jul 19. pii: 452. [Epub ahead of print]14(7):
      Background/Objectives: The increasing prevalence of electronic nicotine delivery systems (ENDS) has prompted questions regarding their effects on periodontal health. While the detrimental impacts of cigarette smoking are well-established, the periodontal implications of ENDS use remain poorly understood. This narrative review aimed to evaluate current evidence comparing periodontal parameters, inflammatory markers, and oral microbiome composition among ENDS users, cigarette smokers, and non-smokers. Methods: A structured literature search was conducted in PubMed (January 2009-May 2026) following a PICO question: "What is the impact of ENDS, compared to cigarette smoking and non-smoking, on periodontal health?" Clinical studies reporting on periodontal health parameters (plaque index, bleeding on probing, probing depth, and clinical attachment loss), inflammatory markers (e.g., IL-1β, IL-6, TNF-α), and microbial composition were included. Due to methodological heterogeneity across studies, meta-analysis was not feasible, necessitating narrative synthesis. Results: Across studies, clinical periodontal findings in ENDS users were heterogeneous and did not consistently resemble those of either cigarette smokers or non-smokers. In contrast, ENDS use was consistently associated with alterations in inflammatory profiles and oral microbiome composition, characterized by selective changes in specific inflammatory cytokines rather than uniform inflammatory upregulation, as well as shifts towards microbial communities linked to periodontal inflammation. Notably, these biological alterations were not uniformly reflected in traditional clinical periodontal indices. Conclusions: ENDS use is associated with heterogeneous clinical findings and inflammatory and microbial alterations that suggest ENDS is a distinct exposure rather than a predictable intermediate between smoking and non-use. This review, to our knowledge, is the first to integrate clinical, inflammatory, and microbiome outcomes and highlights the limitations of relying solely on clinical parameters to assess the impact of ENDS on periodontal health. It also underscores the need for well-designed longitudinal studies to clarify the periodontal implications of ENDS use.
    Keywords:  e-cigarettes; electronic nicotine delivery systems; inflammatory markers; oral microbiome; periodontal disease; vaping
    DOI:  https://doi.org/10.3390/dj14070452