bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2026–06–28
forty-nine papers selected by
Luca Bolliger, lxBio



  1. PLoS Comput Biol. 2026 Jun;22(6): e1014408
      Patients infected with life-threatening multi-drug resistant (MDR) bacteria have been treated with cocktails of bacteriophages. This is a complicated form of personalized medicine as the phages given to a patient have to be selected beforehand on the basis of their lytic capacity of the infecting bacteria. Because bacteria rapidly become resistant, the evolution of resistance to a diverse cocktail of phages is a complicated dynamical process, during which competing bacterial strains replace one another by accumulating several resistance mechanisms, each of which may involve a fitness cost. As a consequence, it is typically not known why a particular phage therapy succeeded or failed, and how one can optimize the composition of the cocktails to maximize the rate of success. To improve upon this, we extend an existing in vivo-calibrated mouse model into a novel mathematical model for the human situation, and include multiple phages infecting multiple bacterial strains, differing in their resistance to each of the phages. We adjust several parameter estimates of the bacterial model to the human situation, and use the model to describe a successful case of phage therapy involving several cocktails, each containing several phages. In the model, treatment success crucially depended on pretreatment resistance levels, and on the diversity and the timing of the cocktails. Once an appropriate cocktail is found, it is less important to further optimize the infection rates of the phages. Resistant bacterial strains expand rapidly when sensitive strains decline, and the higher the infectivity of the phages, the faster resistant strains expand. Because resistance evolves rapidly, it is best to provide a diverse set of phages right from the start of therapy, i.e., to hit hard and early, and create a high genetic barrier to bacterial resistance.
    DOI:  https://doi.org/10.1371/journal.pcbi.1014408
  2. Front Microbiol. 2026 ;17 1865548
       Purpose: The global crisis of antimicrobial resistance has reached critical levels, with multi-drug resistant (MDR) bacterial pathogens threatening to render conventional antibiotics ineffective. This mini review synthesizes recent evidence from 2020 to 2026 on bacteriophage therapy against MDR bacteria, examining clinical applications, engineering advances, mechanistic insights, and emerging technologies.
    Methods: A comprehensive literature search was conducted across Embase, Scopus, and Cochrane Library databases, supplemented by PubMed, Google Scholar, and ArXiv searches, focusing on phage therapy for MDR bacterial infections published between 2020 and 2026.
    Results: Recent developments include expanded clinical experience through specialized phage centers, sophisticated genetic engineering techniques including CRISPR-based systems, successful compassionate-use programs, and innovative combination therapies with antibiotics. Clinical reports demonstrate safety and preliminary efficacy signals in selected refractory infections, though randomized controlled data remain limited. Engineering advances have produced phage-delivered CRISPR antimicrobials, hybrid delivery platforms, and synthetic phage particles that expand therapeutic capabilities.
    Conclusion: While challenges remain in regulatory standardization, scalable manufacturing, and resistance management, the field has demonstrated significant progress toward clinical translation. The convergence of synthetic biology, personalized medicine approaches, and growing clinical evidence positions phage therapy as a viable complementary strategy in the fight against MDR bacterial infections.
    Keywords:  CRISPR-Cas systems; antimicrobial resistance; bacteriophage therapy; combination therapy; multi-drug resistance; phage engineering
    DOI:  https://doi.org/10.3389/fmicb.2026.1865548
  3. Viruses. 2026 Jun 12. pii: 664. [Epub ahead of print]18(6):
      Newborns may suffer from dangerous bacterial infections caused by life-threatening multi-drug resistant pathogens. Thus, despite bactericidal capabilities of antibiotics, microorganisms are known to circumvent this therapy, and a new, more effective type of remedy is needed. An increasingly recognized strategy for addressing these challenges is the use of bacteriophages-viruses infecting bacteria-collectively referred to as phage therapy. Nonetheless, the research considering phage therapy amongst newborns is still at a pioneering stage, owing to the scarcity of systematic investigations and the prevalence of case-study data, leaving room for further discovery and analysis. This review summarizes the information needed to understand this complex issue, considering the description of pathogens causing infections affecting newborns, the formation of the early microbiota and phageome (defining its composition followed by an influence on immune system development), and the possible use of bacteriophages in the treatment, which may be complicated by ethical concerns.
    Keywords:  ESKAPE group; infant microbiota; newborn infections; phage therapy
    DOI:  https://doi.org/10.3390/v18060664
  4. Antibiotics (Basel). 2026 May 25. pii: 537. [Epub ahead of print]15(6):
      Background/Objectives: Biofilms are a form of defense that enables bacteria to withstand antibiotic pressure and demonstrate antibiotic resistance. It is crucial to develop anti-biofilm strategies in order to combat chronic and persistent multidrug-resistant (MDR) infections. Methods: In this study, we developed 3D biofilms of single-, dual-, and poly-species MDR ESKAPE components, including the pathogens P. aeruginosa S. aureus and K. pneumoniae, in CF Mu3Gel. We evaluated the efficacy of using a phage, a di-hetero phage cocktail or a poly-hetero phage cocktail in combination with ciprofloxacin to eliminate mature biofilm biomass after 72 h or one week in a single treatment. Results: The phage components mostly exhibited synergistic behavior when combined with ciprofloxacin and with each other in di- and poly-hetero-cocktails. The reduction in 72-h dual- and poly-species biofilms was one log higher than that of one-week biofilms treated with the phage-antibiotic combination. The greatest reductions were observed in the 72-h single-species biofilm with combination therapy, at 1.4-3.0 log. Reductions of 2.16 and 1.6 log were observed in the dual-species P. aeruginosa and S. aureus biofilm and the poly-species biofilm, respectively. Conclusions: This study examined how a single application of phages or phage cocktails, either alone or in combination with ciprofloxacin, impacted established biofilm models, and how this affected the proportion of microcolonies of different species within each model. These insights will facilitate the development of strategies for multiple follow-up treatments, as well as the reordering of phages, phage cocktails, and combinations with antibiotics, to improve outcomes. The 3D biofilm models developed here could be used to screen phages or phage cocktails either on their own or alongside other therapies. This would facilitate the application of in vitro findings to real physiological settings.
    Keywords:  3D biofilm; combination therapy; persistence; phage hetero-cocktails; phage therapy; phage-phage synergy; phage–antibiotic synergy; poly-biofilm; re-sensitization; synergy level
    DOI:  https://doi.org/10.3390/antibiotics15060537
  5. Diabetes Res Clin Pract. 2026 Jun 23. pii: S0168-8227(26)00310-4. [Epub ahead of print]238 113390
      Diabetic foot ulcers (DFUs) are difficult-to-heal chronic wounds characterized by ischemia, biofilm-associated infection, persistent inflammation, oxidative stress, protease-rich exudate, and abnormal biomechanics. Although hydrogel dressings have been widely explored for DFU management, many reviews remain material-centered and provide limited guidance on clinical scenario matching. This review proposes a microenvironment-informed framework for DFU hydrogel design. We organize hydrogel strategies according to dominant pathological barriers, including impaired angiogenesis, chronic inflammation, oxidative injury, infection, and complex wound geometry, and compare topical/coating, injectable, patch/membrane, microneedle, and 3D-printed systems according to their clinical suitability. Preclinical evidence is synthesized by therapeutic function, while translational barriers such as model heterogeneity, sterilization, batch variability, regulatory classification, and health-economic evidence are critically examined. Pathology-guided bioactivity combined with scenario-matched formulation design may help reposition hydrogel dressings from laboratory constructs toward practical adjuncts in multidisciplinary DFU care.
    Keywords:  Biofilm; Diabetic foot ulcers; Hydrogel dressings; Translational medicine; Wound microenvironment
    DOI:  https://doi.org/10.1016/j.diabres.2026.113390
  6. Medicina (Kaunas). 2026 Jun 10. pii: 1133. [Epub ahead of print]62(6):
      Background and Objectives: This study aims to evaluate the recent literature on the oral-gut connection in the context of periodontal disease, emphasizing the significance of systemic risk associated with chronic inflammation. This review explores whether chronic inflammation resulting from periodontal disease can induce systemic conditions through alterations in the gut microbiome and whether periodontal treatment may contribute to overall health improvement. Materials and Methods: A systematic database search was performed using pre-established search strategies. Searches were conducted in three databases between 1 and 20 October 2025. A total of 578 articles were screened for eligibility based on inclusion and exclusion criteria. Two authors agreed on the selection process used. The methodological quality of the included studies was assessed using the Newcastle-Ottawa scale and the Risk of Bias 2 Tool. Results: Eleven studies were considered eligible for inclusion in the review. The gut microbiome is similar to the oral microbiome in patients with periodontitis. Gut microbial shifts may drive systemic inflammation and metabolic dysfunction. Tooth loss and gum disease are linked to alterations in the gut bacteria, potentially compromising the intestinal barrier permeability. In contrast, the presence of natural teeth may prevent oral-gut bacterial transmission. Changes in the gut microbiota are correlated with improvements in periodontal status after non-surgical periodontal therapy. Conclusions: The evidence presented in this review supports an association between periodontitis, oral-gut microbial alterations, and systemic inflammatory conditions. However, most available studies are observational, limiting causal inference. Targeted modulation of the gut microbiome may represent a promising area for future research, but its clinical applicability remains inconclusive.
    Keywords:  dysbiosis; gut; inflammation; microbiome; periodontitis
    DOI:  https://doi.org/10.3390/medicina62061133
  7. Int J Mol Sci. 2026 Jun 06. pii: 5150. [Epub ahead of print]27(12):
      Systemic antibiotics are among the most widely prescribed therapeutic agents worldwide, and their effects on host-microbe equilibrium extend well beyond the infection for which they are intended. Periodontitis is conventionally framed as a biofilm-initiated, host-mediated inflammatory disease, although recent work has shifted this framework toward microbial homeostasis as a regulator of periodontal stability. We hypothesize that antibiotics are not direct etiologic agents of periodontitis but instead act as risk-modifying factors that lower the threshold at which plaque-mediated inflammation progresses to destructive disease. We propose that this effect may operate through several mechanisms: broad-spectrum or repeated exposure could deplete protective commensals and narrow microbial diversity, creating ecological space for opportunistic and pathogenic taxa; antibiotics may also alter host neutrophil function, cytokine profiles, and antimicrobial peptide regulation and may interfere with the osteoblastic and osteoclastic dynamics governing alveolar bone remodelling; and antibiotic-induced gut dysbiosis may propagate systemic inflammatory signals that further modulate periodontal susceptibility. To evaluate this hypothesis, we synthesize the available clinical, epidemiological, and experimental data across four converging axes-oral microbial ecology, immune regulation, alveolar bone remodelling, and the gut-oral axis-and identify the predictions the hypothesis generates and the evidence gaps it exposes. We emphasize that no clinical study has yet demonstrated a causal link between antibiotic exposure and periodontitis; the framework advanced here is therefore intended to inform antimicrobial stewardship in dentistry and to define a research agenda for determining whether antibiotic exposure constitutes a clinically meaningful modifier of periodontal disease susceptibility.
    Keywords:  antibiotics; bone remodeling; dysbiosis; gut–oral axis; host–microbe interactions; immune regulation; microbial homeostasis; oral microbiome; periodontitis; systemic dysbiosis
    DOI:  https://doi.org/10.3390/ijms27125150
  8. Biomater Adv. 2026 Jun 19. pii: S2772-9508(26)00331-6. [Epub ahead of print]188 215033
      The refractory nature of diabetic foot ulcers (DFUs) stems from persistent immunometabolic dysregulation. Although a myriad of reviews have extensively categorized hydrogel dressings, most remain confined to passive material classifications and isolated phenotypic targets. To bridge this gap, this review delineates an integrated "hydrogel engineering-immunometabolic regulation-tissue regeneration" framework. We redefine hydrogels as "intelligent bioreactors" that actively construct a "pro-healing niche," dissecting the underlying mechano-metabolic crosstalk (e.g., VASP/HIF-1α and mTOR signaling). Furthermore, we elucidate the interventional mechanisms of diverse hydrogel strategies-including externally triggered, dynamically responsive, nanocomposite, and mechanically programmed platforms-across four critical pathways: glycolysis, lipid metabolism, amino acid metabolism, and oxidative stress. Crucially, by extracting raw healing data to calculate relative improvement rates and daily relative improvement rates, we quantitatively benchmark the discrepancies in healing kinetics among distinct strategies. Building upon this, we propose scenario-oriented clinical selection pathways: prioritizing near-infrared (NIR)-responsive or photocatalytic hydrogels for severely hypoxic DFUs, and recommending ultrasound-driven sequential "sterilization-then-antioxidation" hydrogels for neuropathic ulcers complicated by multidrug-resistant bacterial infections. Additionally, via precise metabolic reprogramming, these tailored hydrogels actively drive macrophage repolarization, restore T cell subset balance, and enhance dendritic cell efferocytosis. Finally, by integrating biomarker-driven standardized evaluations, GMP-compliant scale-up engineering, and AI-assisted modular production platforms, this review outlines a step-by-step clinical translational roadmap. This strategic roadmap aims to bridge the gap between laboratory prototypes and personalized precision medicine, ultimately providing a comprehensive blueprint for next-generation metabolic therapeutics in chronic wound management.
    Keywords:  Diabetic foot ulcers; Dynamic metabolic buffering; Immunometabolic reprogramming; Intelligent hydrogels; Macrophage polarization; Pro-healing niche
    DOI:  https://doi.org/10.1016/j.bioadv.2026.215033
  9. Arch Microbiol. 2026 Jun 22. pii: 449. [Epub ahead of print]208(9):
      Polymicrobial communities impose a great challenge for clinical management of chronic infections. It is a consensus now that microbes exist as aggregated colonies shielded within polymeric matrix. Within this matrix more than one bacterial species can exist either in symbiotic or rival relationships. Herein, we investigated the host-specific interspecies interactions between Staphylococcus aureus and Pseudomonas aeruginosa in chronic rhinosinusitis (CRS). The indirect interaction between the two species was assessed using Transwell co-culture chambers, where S. aureus and P. aeruginosa (n = 3 each) derived from CRS patients were cultured in separate chambers that allowed exchange of soluble factors. Later the biofilm biomass of each species was evaluated and compared to single species biofilm. Further, the influence of the co-culture conditions on antibiotic tolerance was evaluated. When derived from the same patient, co-cultured bacteria increased the biofilm biomass of each other significantly by 3.0-4.9 fold (p < 0.01) and exhibited higher tolerance to amikacin compared to co-cultures of isolates from two different patients and monocultured biofilms. Moreover, the incubation of one bacterial protein-enriched secreted fractions (PESF) with alternative species form same patient significantly increased biomass by 1.5-4.8 fold (p < 0.01), while similar trend was not observed among randomly cultured species. These data underscore the synergistic growth pattern between different bacterial species growing in the same niche and highlight the importance of further studies to aid the selection of antibiotics targeting polymicrobial biofilms.
    Keywords:   Pseudomonas aeruginosa ; Staphylococcus aureus ; Antibiotic resistance; Biofilms; Chronic rhinosinusitis
    DOI:  https://doi.org/10.1007/s00203-026-05020-3
  10. Digit Health. 2026 Jan-Dec;12:12 20552076261462641
       Objectives: To develop an evidence-informed, clinically aligned multimodal workflow framework for chronic wound assessment and to identify cross-study patterns in image-based artificial intelligence (AI) applications that inform its design.
    Methods: We conducted a structured evidence mapping and synthesis of published studies on image-based AI for chronic wound assessment. Records were identified through a structured database search and a targeted supplementary search performed during revision. Studies were screened using predefined eligibility criteria, and data were extracted on wound types, image-acquisition approaches, task domains, model architectures, performance measures, and deployment-related characteristics. Cross-study patterns were then used to construct a conceptual workflow framework spanning wound localization, segmentation, clinical interpretation, and longitudinal monitoring.
    Results: A total of 44 studies were included in the final analysis. The evidence base was dominated by diabetic foot ulcer and general chronic wound imaging studies, with more limited representation of pressure injury, venous or vascular wound, and postoperative wound contexts. Camera-based acquisition was the most common imaging approach, while device-based and mobile-based acquisition were less frequently represented. When mapped to workflow-relevant task domains, classification/clinical interpretation and segmentation/measurement were the most strongly represented components, whereas localization/detection and monitoring/prediction were less consistently developed. Cross-study patterns also showed increasing representation of clinically meaningful interpretation tasks, including wound grading, tissue characterization, and infection/ischaemia recognition, as well as emerging use of explainability methods in wound-image analysis. These patterns informed the development of a four-stage clinically aligned multimodal workflow framework for chronic wound assessment.
    Conclusion: Current wound-AI evidence supports a workflow-oriented conceptual model in which wound localization, segmentation, clinical interpretation, and longitudinal monitoring can be organized into a clinically meaningful assessment pathway. The proposed framework is intended as an evidence-informed conceptual structure to guide future multimodal system development, translational research, and prospective validation in real-world wound care settings.
    Keywords:  artificial intelligence; chronic wounds; computer vision; deep learning; digital health; multimodal imaging; tissue classification; wound assessment; wound detection; wound segmentation
    DOI:  https://doi.org/10.1177/20552076261462641
  11. Infect Drug Resist. 2026 ;19 598156
       Background: Purulent pericarditis is a rare, life-threatening infection, most commonly caused by bacteria such as Staphylococcus aureus. We report an exceptional case of hematogenously disseminated infection probably originating from the oral cavity, highlighting a novel pathogen profile.
    Case Presentation: We report a 66-year-old male with no history of periodontal disease or oral procedures presented with purulent pericarditis and a concomitant subphrenic abscess. Metagenomic next-generation sequencing (mNGS) of pericardial fluid revealed a polymicrobial infection with three periodontal pathogens: Tannerella forsythia, Fusobacterium nucleatum, and Porphyromonas gingivalis. The patient was treated with pericardiocentesis, targeted antibiotics, and organ support, resulting in clinical stabilization.
    Conclusion: This case provides clinical evidence that a consortium of periodontal pathogens can disseminate hematogenously to cause severe metastatic infections in sterile sites, even in individuals without overt oral disease. It underscores the need to consider occult oral origins in infections of unknown source and illustrates the value of comprehensive molecular diagnostics in identifying fastidious organisms, although it remains undetermined whether both conditions were secondary to the same source.
    Keywords:  Fusobacterium nucleatum; Porphyromonas gingivalis; Tannerella forsythia; mNGS; purulent pericarditis; subphrenic abscess
    DOI:  https://doi.org/10.2147/IDR.S598156
  12. Antibiotics (Basel). 2026 May 29. pii: 550. [Epub ahead of print]15(6):
      Antimicrobial resistance (AMR) constitutes a critical and escalating global public health challenge, severely limiting the potential of existing antimicrobial drugs and escalating infection-associated morbidity and mortality rates. This analysis focuses on the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), which are prioritized by the World Health Organization (WHO) and represent a significant cause of nosocomial infections due to their extensive drug resistance. We provide an in-depth review of the global prevalence and specific antibiotic-resistant mechanisms of these pathogens. Due to the decline in the traditional antibiotic development pipeline, accelerated development of alternative therapeutic strategies is essential. The review comprehensively discusses innovative non-traditional therapies currently being explored to bypass traditional antibiotic limitations, such as phage therapy, antimicrobial peptides (AMPs), anti-virulence therapies, fecal microbiota transplantation (FMT), and targeted CRISPR-based approaches. Addressing the ESKAPE challenge requires a concerted, multi-sectoral strategy guided by the One Health principle, focusing on enhancing public awareness, improving surveillance and research, optimizing judicious antibiotic use, and cultivating sustainable investment in novel interventions.
    Keywords:  ESKAPE pathogens; antimicrobial resistance (AMR); fecal microbiota transplantation (FMT); methicillin-resistant Staphylococcus aureus (MRSA); vancomycin-intermediate Staphylococcus aureus (VISA); vancomycin-resistant Enterococci (VRE); vancomycin-resistant Staphylococcus aureus (VRSA)
    DOI:  https://doi.org/10.3390/antibiotics15060550
  13. Curr Microbiol. 2026 Jun 24. pii: 452. [Epub ahead of print]83(8):
      Phage therapy is a promising alternative to the growing problem of antibiotic-resistance. However, bacterial phage-resistance may develop, compromising therapy. Phage-resistance has primarily been associated with changes in phage receptors that in the human pathogen, Staphylococcus aureus, are the cell-wall linked wall teichoic acids (WTA) which can be modified by glycosylation. With the aim of identifying factors contributing to phage-resistance, we exposed S. aureus to lytic K-type myo-viruses, namely phage K, ϕIPLA-RODI and Stab21 to obtain resistant clones. Out of 9 phage-resistant mutants, a third harbored mutations in cell-wall genes previously linked to phage resistance, namely in femA, involved in peptidoglycan crossbridge formation, and tagO, encoding the initiator of the WTA biosynthesis. The remaining mutants had mutations in pathways not previously associated with phage-resistance, with three in deoC1 involved in nucleoside catabolism, two in potA and potB, respectively, involved in polyamine import and one in the RNA helicase, cshA. When assessing virulence in Galleria mellonella and antibiotic susceptibility as well as WTA glycosylation, our results showed diverse effects. As expected, mutations in the wall teichoic acid synthesis pathway increased β-lactam sensitivity and attenuated virulence in a G. mellonella model. In contrast, the cshA mutation increased both virulence and susceptibility to β-lactams. Increased virulence was also seen for a mutant with several mutations including femA. Further phage susceptibility appeared not to be strictly correlated with WTA glycosylation patterns. Our findings show that in S. aureus reduced phage susceptibility can be caused by mutations affecting central metabolic processes and can have unpredictable consequences for antibiotic susceptibility and virulence. Our results emphasize the need for evaluating evolutionary trade-offs before clinical phage therapy deployment.
    DOI:  https://doi.org/10.1007/s00284-026-05034-6
  14. Life (Basel). 2026 Jun 11. pii: 989. [Epub ahead of print]16(6):
      Phage therapy is increasingly recognized as a promising alternative to antibiotics for controlling bacterial diseases in aquaculture. This review focuses specifically on sea cucumber farming, with emphasis on phage application methods, therapeutic performance, and current limitations in translating laboratory results into field use. Available studies show that phage-based treatments can improve the survival of Apostichopus japonicus challenged with Vibrio spp., especially when delivered through feed or formulated as phage cocktails. However, practical application is still constrained by host-range specificity, phage resistance, environmental stability, delivery efficiency, and regulatory barriers. By summarizing recent evidence and identifying research gaps, this review highlights the potential of phage therapy as a sustainable disease management strategy for sea cucumber aquaculture.
    Keywords:  aquaculture health management; biocontrol strategies; disease outbreaks; environmental safety; phage application; phage cocktails
    DOI:  https://doi.org/10.3390/life16060989
  15. Pathogens. 2026 May 22. pii: 559. [Epub ahead of print]15(6):
      Bacterial sexually transmitted and sexually associated infections remain a major global health concern, increasingly complicated by antimicrobial resistance and the limited effectiveness of existing therapies. In this context, bacteriophage-based and phage-derived approaches have re-emerged as potential alternative antibacterial strategies. This narrative review examines their applicability across key bacterial pathogens associated with sexually transmitted infections, including Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Treponema pallidum and biofilm-associated bacterial vaginosis, with a particular focus on pathogen-specific biological barriers. Available evidence indicates that the success of phage-based interventions is strongly dependent on factors such as intracellular localisation, structural characteristics of the bacterial envelope and the presence of polymicrobial biofilms. While phage-derived platforms, including endolysins, depolymerases and engineered phages, demonstrate antibacterial activity in experimental settings, their effectiveness is uneven across different pathogens. Biofilm-associated infections appear more accessible to these approaches, whereas intracellular and structurally atypical bacteria are currently considered more challenging targets based on available mechanistic and experimental evidence. These observations highlight the need for pathogen-specific engineering strategies and delivery systems. Overall, phage-based therapeutics in this field should be considered within a framework that integrates biological constraints with targeted antimicrobial design.
    Keywords:  CRISPR-Cas; Chlamydia trachomatis; Mycoplasma genitalium; Neisseria gonorrhoeae; Treponema pallidum; antimicrobial resistance; bacterial vaginosis; bacteriophage therapy; endolysins; sexually transmitted infections
    DOI:  https://doi.org/10.3390/pathogens15060559
  16. Front Cell Infect Microbiol. 2026 ;16 1805111
       Introduction: Diabetic foot ulcers (DFUs) are serious complications of type 2 diabetes and are frequently infected with Staphylococcus aureus. However, the virulence mechanisms that enable S. aureus to adapt to diabetic conditions and drive disease progression remain unclear.
    Methods: To investigate the relationship between S. aureus virulence and DFU severity, we freshly isolated S. aureus from DFU patients with clinical severities ranging from Grade 2 (mild) and Grade 4 (severe). We evaluated their virulence characteristics using in vitro assays and an in vivo diabetic pressure wound infection model in diabetic TALLYHO/JngJ mice.
    Results: S. aureus isolates from Grade 4 DFUs exhibited significantly greater biofilm formation, hemolytic activity, and resistance to oxidative stress compared to Grade 2 isolates. In the in vivo diabetic pressure wound infection model, Grade 4 isolates induced significantly greater tissue necrosis and delayed wound healing, accompanied by sustained expression of pro-inflammatory M1 macrophage-associated genes (NOS2, IL1B, and IFNG). In contrast, Grade 2 isolates caused minimal tissue necrosis and promoted rapid wound healing with expression of anti-inflammatory M2 macrophage-associated genes (ARG1, IL4, and IL10).
    Discussion: Collectively, these findings demonstrate that highly virulent S. aureus strains associated with severe DFUs exhibit enhanced virulence traits that promote host colonization and immune responses skewing macrophage polarization toward a sustained pro-inflammatory M1 phenotype, thereby exacerbating tissue damage and impairing wound healing. These virulence characteristics may serve as functional biomarkers to distinguish pathogenic S. aureus from less pathogenic or opportunistic S. aureus strains in DFUs.
    Keywords:  Staphylococcus aureus; diabetic foot ulcer; diabetic murine model; macrophage polarization; virulence; wound healing
    DOI:  https://doi.org/10.3389/fcimb.2026.1805111
  17. Microbiologyopen. 2026 Jun;15(3): e70349
      Modern technological advances have revealed that the lungs, once believed to be sterile, actually harbor a diverse community of microorganisms. A normal lung microbiome possesses its own characteristic microbial community, although it is largely influenced by the microbiota of the upper respiratory tract. The lung microbiome is distinct from that of other organs due to unique selective pressures, including mechanical clearance through coughing, the activity of pulmonary macrophages, the coordinated movement of respiratory cilia, and the antimicrobial effects of alveolar surfactant. Although recent research has largely concentrated on the pulmonary bacteriome, comparatively little attention has been given to the lung mycobiome and virome. Various databases such as PubMed, Scopus/Web of Science, Google Scholar, and Medline for literature research up to December 2025. This updated review discusses the origin, composition, and functional significance of the lung microbiome, with particular emphasis on its protective role against respiratory pathogens through host-microbe interactions. The review primarily focuses on respiratory disorders such as asthma, along with a range of viral and bacterial infections. Special attention is given to current evidence on how lung microbial communities influence susceptibility to pulmonary infections, as well as how the lung microbiome contributes to host defense during infectious conditions.
    Keywords:  bacteriome; immunity; infections; lungs; microbiome; virome
    DOI:  https://doi.org/10.1002/mbo3.70349
  18. Curr Issues Mol Biol. 2026 May 29. pii: 574. [Epub ahead of print]48(6):
      Periodontal disease is a chronic inflammatory condition driven by polymicrobial biofilms whose interaction with the host immune response drives the destruction of tooth-supporting tissues. Within these communities, bacterial cell-cell communication-particularly quorum sensing (QS)-coordinates virulence factor expression, biofilm maturation, and interspecies behaviour, allowing pathogens to mount population-dependent attacks on the host. Disrupting these signals has therefore drawn growing attention as an anti-virulence strategy for biofilm-associated oral infection. Quorum quenching (QQ)-the inhibition or disruption of QS pathways-prevents bacteria from coordinating these virulence-related activities. The candidate inhibitors investigated to date fall into three broad classes: conventional antibiotics used at sub-inhibitory concentrations, plant-derived natural compounds, and synthetic molecules designed to interfere with signal synthesis, signal reception, or signal transduction. In experimental work on periodontal pathogens, agents from each class reduce biofilm formation, suppress virulence factor production, and disrupt microbial communication within polymicrobial biofilms. Clinical translation, however, lags behind the laboratory evidence. Most data still come from in vitro systems and animal models, and the ecological complexity of the oral biofilm makes therapeutic targeting difficult: signals that drive virulence in pathogens also support cooperation among commensals. Toxicity profiles, pharmacokinetics, and well-powered clinical trials are needed before quorum-quenching agents can be considered for routine periodontal care. Even with these caveats, targeting bacterial communication offers a different therapeutic logic from conventional antimicrobials: attenuating virulence rather than killing cells, and so exerting weaker selective pressure for resistance. Further dissection of QS networks in oral biofilms-and the rational design of quenching agents that act on pathogenic rather than commensal signalling-may yield useful adjuncts to current periodontal therapy.
    Keywords:  biofilm; periodontal disease; periodontal pathogens; quorum quenching; quorum sensing; quorum-sensing inhibitors
    DOI:  https://doi.org/10.3390/cimb48060574
  19. Curr Res Microb Sci. 2026 ;11 100618
      Mucosal barriers serve as a multifunctional interface and nutrient-rich habitat for diverse microbes, including bacteria and bacteriophages. Some phages can bind to mucin glycoproteins via carbohydrate-interacting modules and provide an additional layer of mucosal immunity by shielding the underlying epithelium from invading bacteria. However, the role of mucins in shaping phage-bacterium interactions remains poorly understood. We investigated dynamics between highly pathogenic Yersinia enterocolitica serotype O:8 and its mucus-adherent phage fMtkYen801 under the in vitro mucosal environment. We assessed how mucin supplementation, varying phage doses, nutrient and temperature conditions influence phage-bacterium dynamics and biofilm development. We found that bacterial pre-exposure to mucins led to enhanced phage replication, with a 2-log increase in phage titers. Mucins also modulated post-infection growth dynamics and reduced biofilm formation in the host bacteria. Genomic analysis of phage resistant bacterial variants revealed mutations in virulence, quorum sensing and antibiotic resistance genes in both mucin enrichment and control groups, suggesting potential fitness tradeoffs during resistance evolution. These findings highlight the role of mucosal environments in shaping phage-host interactions in Y. enterocolitica, a significant enteric pathogen, and emphasize the need for investigating these dynamics under complex, physiologically relevant systems to inform better phage therapy strategies against mucosal bacterial infections.
    Keywords:  Bacteriophage adherence to mucus (BAM); Mucosal environment; Phage-host interactions; Y. enterocolitica
    DOI:  https://doi.org/10.1016/j.crmicr.2026.100618
  20. Front Microbiol. 2026 ;17 1849761
       Introduction: Klebsiella pneumoniae (Kpn) is the second most frequent cause of urinary tract infections (UTIs) and represents a major concern in the context of antimicrobial resistance (AMR); nevertheless, the phenotypic and genomic traits that define uropathogenic Kpn strains are not clear.
    Methods: In this study, 24 carbapenemase-producing Kpn strains, most of them (23/24) carrying bla OXA-48, isolated from urine samples of nosocomial or community origin in northwest Spain, were characterized in terms of antibiotic resistance, virulence traits and biofilm-forming capacity to identify UTI-associated traits. Additionally, the susceptibility to bacteriophages, both in planktonic cultures and biofilms, was assessed.
    Results and discusion: High levels of resistance to other antibiotics were also observed, with 83.3% of strains classified as multidrug-resistant. Most isolates belonged to ST15 (n = 11) and ST147 (n = 8), representing high-risk clones, all of them harboring bla OXA-48. Strain 6022, belonging to ST307, represented a third high-risk clone. Principal component analysis (PCA) revealed clustering of strains into two main groups according to antibiotic resistance and virulence genes, corresponding to the two predominant STs. None of the urine strains carried hypervirulence-associated genetic markers, despite the high proportion of hypermucoviscous isolates. Six lytic bacteriophages belonging to the genera Webervirus, Jiaodavirus, and Druslisvirus, were evaluated against the Kpn isolates. All six phages lysed at least one strain. None of the phages lysed ST15 isolates, confirming previously reported specificity associated with ST and capsule locus types. The combination of Webervirus kpv33d1 and Jiaodavirus kpv33d6 completely inhibited planktonic growth of selected strains, even at low multiplicities of infection (MOI = 0.01). Importantly, this low MOI was sufficient to significantly reduce colony-forming unit counts in preformed biofilms, a key factor in infection persistence and antibiotic resistance in Kpn. These results indicate that some genomic and phenotypic traits seem to be associated with UTI Kpn strains, even though a higher number of strains should be analyzed. The isolation of wide-spectrum phages for the treatment of Kpn UTI infections is demonstrated to be feasible, but our results emphasize the need to assess biofilm-disrupting activity when selecting phages for therapeutic applications against K. pneumoniae.
    Keywords:  Klebsiella pneumoniae; MDR; OXA-48; UTI; bacteriophage; biofilm; carbapenemase; urinary tract infection
    DOI:  https://doi.org/10.3389/fmicb.2026.1849761
  21. Cureus. 2026 May;18(5): e109402
      Alzheimer's disease (AD) and periodontitis are prevalent chronic conditions that disproportionately affect aging populations and pose substantial public health challenges worldwide. Increasing evidence suggests a potential association between these two diseases, with chronic oral infection and systemic inflammation emerging as key linking mechanisms. Periodontitis is characterized by a dysbiotic oral microbiome and persistent inflammatory responses that can lead to the dissemination of periodontal pathogens and their virulence factors into the systemic circulation. Notably, some studies have reported the detection of pathogens such as Porphyromonas gingivalis and their toxic products in the brains of individuals with AD, implicating a possible role in neuroinflammation and neurodegeneration. However, it should be clarified that detection does not establish causation. This narrative review aims to synthesize the existing evidence from animal studies exploring the link between periodontitis and AD and its related mechanisms, including neuroinflammation, amyloid and tau pathology, blood-brain barrier dysfunction, and systemic interactions. The electronic search in PubMed yielded 585 results. We focused on the past 10 years, thus removing 114 results. A total of 471 studies remained. Of the 471 articles reviewed, 239 studies were excluded based on their titles, abstracts, publication types, and topics because of inappropriate study designs (i.e., designs other than cross-sectional or animal studies). A total of 232 studies were further investigated. In this review, the analysis focused exclusively on animal studies, and the full texts were assessed against predefined eligibility criteria focusing on study design, animal model, periodontal exposure, and AD-related outcomes. Studies that met all inclusion criteria were included, whereas articles with inappropriate study designs or irrelevant outcomes were excluded. After full-text screening, 101 studies remained. Preclinical (animal) evidence supported plausible mechanistic links between periodontitis and AD. Furthermore, oral pathogens appear to mediate this ongoing neuroinflammation.
    Keywords:  alzheimer’s dementia; alzheimer’s-related disease; chronic generalized periodontitis; oral-systemic connection; periodontal status
    DOI:  https://doi.org/10.7759/cureus.109402
  22. Eur J Oral Sci. 2026 Jun 26. e70120
      The 2018 AAP/EFP Classification of Periodontal Diseases introduced staging and grading to improve the description of periodontitis severity and factors associated with disease progression. Although widely adopted in clinical and research settings, its validation has focused mainly on inter-examiner agreement, diagnostic concordance and prognostic performance, with limited evidence on patient-centred outcomes such as comprehension, recall and behavioural relevance. Available studies suggest that patients retain staging and grading poorly and instead rely on observable and functional indicators of disease, indicating a potential mismatch between clinical constructs and patient-relevant information for decision-making. This article examines the 2018 classification from a communication perspective, distinguishing diagnostic validity from communicative validity and evaluating whether extent, stage and grade can meaningfully support patient understanding. A pragmatic conceptual model reframes these constructs as communication components describing disease distribution, current burden and progression risk. Overall, although the 2018 system provides a structured framework for periodontal classification, its effectiveness as a communication tool remains uncertain. Future research should investigate how periodontal information can be structured to improve comprehension, recall and informed decision-making in practice.
    Keywords:  patient compliance; patient education; periodontitis/classification; periodontitis/diagnosis; periodontology
    DOI:  https://doi.org/10.1111/eos.70120
  23. J Periodontal Res. 2026 Jun 22.
      Periodontal diseases, including both gingivitis and periodontitis, occur commonly among pregnant individuals. Both gingivitis and periodontitis are associated with adverse pregnancy outcomes (APOs) such as early pregnancy loss, preterm birth, preeclampsia, low birth weight, and stillbirth. This review highlights that the strongest mechanistic evidence linking periodontal diseases with APOs involves the domains of systemic inflammation, including increased pro-inflammatory cytokines and activation of matrix metalloproteases associated with preterm labor, and microbial translocation involving hematogenous dissemination of periodontopathic bacteria to the fetoplacental unit. Yet, other mechanistic domains remain underexplored, including maladaptive myelopoiesis with alterations of neutrophil activity, immune player trafficking with autoantibody development, masticatory dysfunction-diet interactions that may further increase risk of critical vitamin and nutritional deficiencies related to both periodontitis and APOs, and functional dysregulation of the oral microbiome including generation of nitric oxide that could impact pregnancy outcomes. Additionally, specific underlying vulnerabilities unique to pregnancy such as increased hormone production such as progesterone and cortisol likely impact the risk of periodontal diseases in pregnancy. By delving into these critical mechanistic domains, this review reveals both current understanding and critical areas for future research to overcome deficits in knowledge pertaining to how periodontal diseases in pregnancy lead to APOs. Elucidating these novel insights can promote scientific advancement, facilitate the development of novel interventions that prevent and/or treat periodontal diseases in pregnancy, and concurrently improve the lives and well-being of pregnant individuals and their children worldwide.
    Keywords:  adverse pregnancy outcomes; gingivitis; mechanistic studies; periodontal diseases; periodontitis; pregnancy; preterm birth
    DOI:  https://doi.org/10.1111/jre.70134
  24. Arch Oral Biol. 2026 Jun 19. pii: S0003-9969(26)00174-3. [Epub ahead of print]190 106668
       OBJECTIVE: This scoping review aimed to map and synthesize the available evidence linking periodontal pathogen-derived endotoxemia and bacteremia to liver abnormalities and to identify the biological mechanisms potentially involved in hepatic injury.
    DESIGN: Following PRISMA-ScR guidelines, comprehensive electronic searches were conducted across major databases, including MEDLINE, Embase, Scopus, Web of Science, and Cochrane CENTRAL, complemented by grey literature sources. Experimental and clinical studies reporting endotoxemia and/or bacteremia attributable to periodontal pathogens in association with liver-related outcomes were included without restrictions on study design or language. Data extraction and study selection were performed in duplicate. Methodological appraisal was conducted using the SYRCLE risk of bias tool for animal studies and the Joanna Briggs Institute checklist for case reports.
    RESULTS: Twenty studies met the inclusion criteria, comprising experimental animal studies and clinical case reports. Porphyromonas gingivalis was the most frequently investigated pathogen, followed by Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum. Experimental evidence consistently demonstrated that periodontal pathogen-derived endotoxemia and bacteremia promote hepatic inflammation, oxidative stress, lipid dysregulation, steatosis, hepatocyte injury, and fibrogenic remodeling. Reported mechanisms included activation of Toll-like receptor signaling, Galectin-3 accumulation, TGF-β1/Smad-mediated fibrogenesis, hepatic stellate cell activation, and endoplasmic reticulum stress. Clinical reports further linked odontogenic infections to severe hepatic complications, including pyogenic liver abscesses and cirrhosis.
    CONCLUSION: The available evidence supports a biologically plausible role for periodontal pathogen-derived endotoxemia and bacteremia in the initiation and progression of liver disease. However, the current evidence base is predominantly preclinical, highlighting the need for well-designed human studies to establish causality and clinical relevance.
    Keywords:  Metabolic dysfunction-associated steatotic liver disease; pathogenesis; periodontal disease, metabolic dysfunction-associated steatohepatitis; periodontitis fatty liver
    DOI:  https://doi.org/10.1016/j.archoralbio.2026.106668
  25. Curr Diabetes Rev. 2026 Jun 23.
      Diabetic foot ulcers are severe complications of diabetes mellitus; they are characterized by chronic inflammation, poor wound healing, and high risks of infection leading to extended hospitalizations and amputation. Although progress has been made in the conventional care of wounds, current therapies still fall short in yielding optimal healing outcomes. In recent years, bioactive natural products and phytochemicals have emerged as promising therapeutic agents due to their diverse pharmacological properties, including anti-inflammatory, antioxidant, antimicrobial, and pro-angiogenic effects. Key active phytochemicals such as curcumin, quercetin, resveratrol, and berberine have been investigated for their potential to enhance wound closure, modulate immune function, and promote tissue regeneration. A literature review was conducted through a systematic search of electronic databases, including PubMed/MEDLINE, Scopus, Web of Science, ScienceDirect, and Google Scholar, using keywords such as "diabetic foot ulcers," "phytochemicals," "natural products," "wound healing," and "drug delivery systems." Many phytochemicals have been reported for their efficacy in DFU models, modulating oxidative stress, stimulating fibroblast proliferation, enhancing collagen synthesis, and inhibiting the growth of microbial biofilms. Advanced drug delivery platforms have been developed to improve the solubility, stability, and targeted delivery of these compounds to the site of injury, utilizing hydrogels, nanoparticles, and polymer-based scaffolds. Preclinical and some clinical studies support the therapeutic potential of these agents; however, translational challenges persist due to issues with formulation, standardization, and the need for large-scale clinical validation. Phytochemical-based interventions are, therefore, a promising complementary approach for treating DFUs. The integration of these natural agents into conventional wound care regimens can improve healing outcomes and reduce complications. Future studies should focus on well-designed clinical trials, detailed mechanistic studies, and standardized and scalable delivery systems to support the clinical translation of phytochemical therapies in DFU management.
    Keywords:  Diabetic Foot Ulcers (DFUs); antimicrobial and anti-inflammatory agents; nanocarrier drug delivery; natural products therapy; phytochemicals; wound healing
    DOI:  https://doi.org/10.2174/0115733998431722260327100634
  26. Oral Health Prev Dent. 2026 Jun 25. 24 461-472
       PURPOSE: This systematic review aimed to investigate a potential association between ankylosing spondylitis (AS) and periodontitis (PD), two chronic inflammatory diseases.
    METHODS AND MATERIALS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, searches were conducted in PubMed, The Cochrane Library, Scopus, and Web of Science. Keywords included 'spondyloarthritis', 'ankylosing spondylitis', 'periodontal diseases', and 'periodontitis'. Study selection was performed by independent authors, and quality was assessed using Scottish Intercollegiate Guidelines Network (SIGN) methodology and the STROBE-MR statement.
    RESULTS: Out of 255 initial studies, 18 eligible studies (3 cohort, 14 case-control, 1 Mendelian randomisation) were selected, all of acceptable to high quality. The prevalence of PD in AS patients showed conflicting results. Periodontal parameters like bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment loss (CAL) didn't consistently show statistically significant differences but were frequently correlated with AS parameters (eg, MASES, BASDAI, BASFI, CRP, AS duration). AS treatment with anti-TNF-α agents was associated with a decrease in PPD and CAL. Other findings included an increase in Gingival Index in AS patients treated with anti-TNF-α and mixed results for the Decayed, Missing, and Filled Teeth Index. Microbiological studies showed inconsistent results for Porphyromonas gingivalis (Pg), but anti-Pg IgG levels correlated with AS parameters. PD appeared to significantly increase inflammatory markers (IL-6, TNF-α, CRP, ESR) in AS patients. Only one study investigated a genetic association, finding none.
    CONCLUSION: A definitive conclusion regarding an increased prevalence of PD in AS patients cannot be drawn with certainty from this review, possibly due to heterogeneous classification criteria. However, the correlation between PD and AS parameters, alongside the impact of AS therapy on periodontal health, is noteworthy. Screening and treating periodontal disease in AS patients might delay symptom progression and reduce drug dosage, though targeted clinical trials are necessary to confirm these findings.
    Keywords:  ankylosing spondylitis; periodontal diseases; periodontitis; spondyloarthritis; systematic review
    DOI:  https://doi.org/10.3290/j.ohpd.c_2747
  27. Microbiol Resour Announc. 2026 Jun 22. e0128025
      With the purpose of finding phages that can target Manitoba farm isolates of Streptococcus suis, we began the characterization of a control strain, Streptococcus sp. bacteriophage 118 (ATCC 19951-B2). Here we describe the genome sequencing and reclassification of the 154,261-bp virus as an Enterococcus phage.
    Keywords:  bacteriophage genetics; bacteriophages
    DOI:  https://doi.org/10.1128/mra.01280-25
  28. Microbiologyopen. 2026 Jun;15(3): e70344
      The escalating threat of antimicrobial resistance has renewed global interest in bacteriophages as precise and powerful tools for controlling bacterial populations in the human gut. These viruses owe much of their antibacterial potential to phage-encoded endolysins, enzymes capable of rapidly degrading bacterial cell walls with high specificity and low potential for resistance development. Despite their therapeutic promise, the overall composition of the gut phageome and the structural modularity of its endolysins remain poorly understood. In this study, we performed a large-scale analysis of 9141 human gut metagenomic samples from 34 independent studies. Using standardized workflows for assembly, genome clustering, host prediction, and protein domain annotation, we reconstructed 15,267 phage genomes and identified 3794 corresponding endolysins. The recovered genomes showed substantial variation in size and coding density, with an average GC content of 43%. Host prediction indicated that most phages targeted bacterial members of the phyla Bacillota (41%) and Bacteroidota (23%). Endolysin sequences grouped into 296 protein families and displayed striking domain modularity. Catalytic domains such as Amidase_2 and Glyco_hydro_25 frequently co-occurred with cell wall-binding motifs including LysM and CW_7. Remarkably, one endolysin contained 15 distinct domains, the highest natural domain diversity reported to date. Collectively, this study represents the most comprehensive characterization of the human gut phageome and its encoded endolysins to date. The exceptional modular diversity uncovered highlights the gut phageome as a rich reservoir of endolysin variants, providing a strong foundation for developing next-generation therapeutics against multidrug-resistant bacterial pathogens.
    Keywords:  antimicrobial resistance; endolysins; human gut phageome; metagenomics; modular enzymes
    DOI:  https://doi.org/10.1002/mbo3.70344
  29. Microorganisms. 2026 May 27. pii: 1213. [Epub ahead of print]14(6):
      Salmonella enterica serovar Enteritidis is a leading cause of foodborne zoonoses worldwide. The rapid emergence of multidrug-resistant (MDR) strains has compromised traditional antimicrobial therapies, necessitating the development of biosafe alternatives such as bacteriophages. This study aimed to isolate and comprehensively characterize novel lytic bacteriophages targeting multidrug-resistant Salmonella enterica subspecies enterica serovar Enteritidis isolates from Lebanon. In this study, four novel Salmonella phages, EDA02, EDA03, EDA05, and EDA06, were isolated from wastewater and poultry effluents in Lebanon. The isolates were characterized using host range profiling, one-step growth kinetics, and physicochemical stability assays. Comprehensive whole-genome sequencing (WGS) and phylogenetic analyses were performed to assess their genomic safety and taxonomic placement. Phages EDA03 and EDA06 exhibited the broadest intra-serovar lytic activity within the tested panel, infecting up to 72% and 67% of the MDR isolates, respectively. One-step growth analysis revealed latent periods of 30-40 min, with burst sizes ranging from 6.0 to 150 phages/infected cell. All four phages demonstrated robust stability across pH 4.7-10.3 and temperatures from 4 °C to 50 °C. WGS revealed genome sizes ranging from 42.3 kb to 108.8 kb, with no identified genes associated with lysogeny, virulence, or antimicrobial resistance. Phylogenomic analysis assigned all isolates to the family Straboviridae, with <95% intergenomic similarity to their closest RefSeq relatives, supporting their classification as novel species. The isolated phages demonstrate substantial lytic activity and environmental resilience under the tested conditions. Their complementary lytic profiles, environmental resilience, and genomic safety support their further evaluation as biocontrol candidates. This study represents the first genomic and phenotypic characterization of anti-Salmonella Enteritidis phages from Lebanon. These findings support the development of phage-based interventions for food safety and antimicrobial resistance mitigation in resource-limited settings.
    Keywords:  Salmonella enterica; bacteriophage; biocontrol; multidrug resistance; therapy
    DOI:  https://doi.org/10.3390/microorganisms14061213
  30. iScience. 2026 Jul 17. 29(7): 116016
      Pseudomonas aeruginosa (Pa) and Staphylococcus aureus (Sa) co-infection has been associated with worse clinical outcomes in people with cystic fibrosis (pwCF); however, the nature of their interaction is poorly understood. This was a 3-year prospective study of pwCF with chronic Pa infection. Pa, Sa,and staphylococcal protein A (SpA) were visualized by confocal microscopy in sputum samples obtained at baseline, exacerbation, after antibiotic treatment,and recovery. Forty-five participants were enrolled. At exacerbation, Pa biovolume and aggregate number increased in children, as well as geospatial distancing of Pa from Sa. With IV antibiotics, Pa (0.5-20 μm diameter) decreased significantly more than large Pa aggregates (>20 μm). Increasing sputum SpA concentrations were correlated with higher Pa biovolume in children (p = 0.04, r = 0.54). Within CF airways, Pa and Sa occupy spatially distinct niches but may interact through SpA production in children. Large Pa aggregates persisted despite antibiotics, indicating sustained infection.
    Keywords:  bacteriology; immune response; microbiofilms
    DOI:  https://doi.org/10.1016/j.isci.2026.116016
  31. Gut Microbes. 2026 Dec 31. 18(1): 2689168
      Cross-kingdom dysbiosis of the gut microbiome along the gut-lung axis has emerged as a key driver of chronic and acute respiratory diseases. Beyond bacteria, the intestinal mycobiome and virome, including bacteriophages, shape mucosal immunity and metabolism through partially overlapping but non-redundant pathways. In this Review, we synthesize rapidly expanding evidence that fungi, bacteria, and phages in the gut form an integrated network that may influence susceptibility, inflammatory tone, and therapeutic responsiveness across asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), and lung cancer via the gut-lung axis. We first summarize how cross-kingdom communities in the intestine are organized and interact, highlighting a tripartite framework centered on pathogen-associated molecular pattern-pattern recognition receptor (PAMP-PRR) circuits, the short-chain fatty acid (SCFA)-regulatory T-cell axis, and tryptophan-indole-aryl hydrocarbon receptor (AHR) signaling. We then compare how these shared axes are differentially perturbed across asthma, COPD, ARDS, and lung cancer, using these disorders as representative but non-sequential disease contexts along a conceptual gradient of immune-microecological disruption. Finally, we discuss how dietary modulation, pre-/pro-/postbiotics, mycobiome- and virome-targeted strategies, and phage-based approaches could be rationally combined to restore gut-derived immunometabolic circuits and improve respiratory outcomes. By integrating cross-kingdom ecology with mucosal immunology, this Review provides an integrative interpretive framework suggesting that gut microbiome-targeted strategies may help refine prevention, stratification, and adjunctive treatment approaches in selected respiratory disease contexts.
    Keywords:  Gut microbiome; bacteriophages; cross-kingdom interactions; gut–lung axis; lung diseases; mycobiome; virome
    DOI:  https://doi.org/10.1080/19490976.2026.2689168
  32. Life (Basel). 2026 May 29. pii: 920. [Epub ahead of print]16(6):
      Microbiome dysbiosis has become recognized as an important interface connecting environmental exposures to chronic inflammatory and degenerative diseases. Although prior research has largely considered heavy metals as biomarkers of exposure and toxicity, their function as ecological modulators of host-associated microbial communities remains underexplored. The oral cavity is a distinct exposome-microbiome interface where environmental, behavioral, and intraoral metal sources converge and interact with structured biofilms and mucosal immunity. This review adopts an ecological systems perspective, interpreting chronic low-dose exposure to metals such as cadmium, lead, mercury, nickel, chromium, arsenic, and aluminum as a sustained selective force on oral microbial networks. A resilience-threshold model is proposed in which cumulative metal pressure progressively diminishes microbial community stability, alters network topology, and drives transitions toward persistent dysbiosis. These modifications are further reinforced by oxidative-inflammatory feedback loops at the host-microbiome interface, facilitating a self-sustaining ecological imbalance. Sketching on insights from microbial ecology, environmental toxicology, and host response biology, this review presents a framework that links metallomic patterns to microbial restructuring, redox imbalance, immune activation, and regulatory adaptation. The analysis emphasizes ecological perturbations from stable dysbiotic states and identifies key methodological limitations that currently restrict causal inference. By conceptualizing heavy metals as active ecological drivers rather than passive exposure indicators, this work establishes a foundation for understanding microbiome-mediated disease susceptibility within an exposome-informed systems biology framework.
    Keywords:  biofilm ecology; dysbiosis; environmental exposure; heavy metals; inflammation; metal resistance genes; multi-omics biomarkers; oral microbiome; oxidative stress; salivary metallomics
    DOI:  https://doi.org/10.3390/life16060920
  33. Front Oral Health. 2026 ;7 1706821
       Background: Emerging evidence highlights a pathophysiological interplay between periodontitis and non-alcoholic fatty liver disease yet the mechanistic underpinnings and therapeutic implications remain contentious. This review systematically elucidates molecular crosstalk through the "oral-gut-liver axis" and "oral-liver axis".
    Methods: A comprehensive literature review was conducted using PubMed, Scopus and Web of Science, employing keywords related to periodontal disease and non-alcoholic fatty liver disease.
    Results: Analysis of 16 original studies revealed that periodontitis and its associated pathogens promote the progression of non-alcoholic fatty liver disease through multiple pathways: (1) activation of hepatic inflammatory responses (elevated IL-6, IL-17, and TNF-α levels), (2) exacerbation of metabolic dysregulation (increased HOMA-IR, ALT, and AST), and (3) disruption of the oral-gut-liver axis. Notably, non-surgical periodontal therapy demonstrated therapeutic potential by simultaneously improving periodontal health and attenuating non-alcoholic fatty liver disease progression through reduction of hepatic pro-inflammatory cytokines and fibrogenic mediators.
    Conclusions: Periodontitis may exacerbate systemic inflammation via the oral-liver and oral-gut-liver axes, inducing insulin resistance and promoting non-alcoholic fatty liver disease. Non-surgical periodontal therapy can improve non-alcoholic fatty liver disease, but methodological heterogeneity in current studies necessitates further prospective research to clarify their relationship.
    Keywords:  NAFLD; Porphyromonas gingivalis; oral-gut-liver axis; periodontitis; systemic inflammation
    DOI:  https://doi.org/10.3389/froh.2026.1706821
  34. Antibiotics (Basel). 2026 Jun 17. pii: 617. [Epub ahead of print]15(6):
      Background/Objectives: Antimicrobial resistance in pediatric infections presents a worsening global public health challenge, with antimicrobial resistance (AMR) accounting for more than one million deaths annually and disproportionately affecting children younger than 5 years of age. Neonates and critically ill children face heightened risk owing to immature immunity, frequent healthcare exposures, and limited therapeutic options. This review synthesizes evidence on the epidemiology, mechanisms of resistance, clinical outcomes, and management of AMR across the full pediatric age range. Methods: PubMed/MEDLINE and Google Scholar were searched for literature from 2014 to 2026 using terms covering antibiotic resistance, pediatric populations, and key pathogens. Approximately 1840 records were screened; 69 sources met all inclusion criteria. A narrative synthesis approach was used, given heterogeneity across study designs and outcomes. Results: Extended-spectrum β-lactamase (ESBL)-producing Enterobacterales, carbapenem-resistant pathogens, and methicillin-resistant Staphylococcus aureus drive substantial morbidity and mortality in children. Approximately one in five pediatric Gram-negative bloodstream isolates are resistant to third-generation cephalosporins, a phenotype independently associated with a roughly three-fold increase in adjusted mortality. Carbapenem-resistant Klebsiella pneumoniae bacteremia carries a 30-day mortality approaching 40%, and isolates in low- and middle-income countries (LMICs) frequently harbor multiple resistance genes. Pneumococcal conjugate vaccine implementation was associated with absolute reductions of 7-11% in the proportion of pediatric pneumococcal isolates that were penicillin-non-susceptible or penicillin-resistant, largely by preventing infections caused by resistant serotypes and by reducing antibiotic selection pressure, rather than through a direct effect on resistance mechanisms; global AMR mortality in children younger than 5 years of age fell by more than 50% between 1990 and 2021. Conclusions: Pediatric AMR reflects intersecting microbiological, clinical, and health-system challenges. Priority actions include scaling antimicrobial stewardship programs, expanding access to rapid molecular diagnostics, integrating whole-genome sequencing into surveillance, conducting pediatric-inclusive randomized trials, and deploying vaccines as primary prevention tools, with particular emphasis on LMICs where the burden is greatest.
    Keywords:  ESBL; MRSA; antibiotic resistance; antimicrobial stewardship; carbapenem resistance; multidrug-resistant organisms; pediatric infections; pneumococcal conjugate vaccine
    DOI:  https://doi.org/10.3390/antibiotics15060617
  35. Cell Host Microbe. 2026 Jun 26. pii: S1931-3128(26)00224-6. [Epub ahead of print]
      Antibiotics are among medicine's greatest successes, but resistance evolution threatens their continued efficacy. Decades of research have deepened our understanding of the mechanisms and evolutionary dynamics of antimicrobial resistance. More recently, advances in machine learning (ML) and artificial intelligence (AI) show promise in predicting antimicrobial resistance in pathogens based on rapid whole-genome sequencing and other accessible data. In this perspective, we highlight advances in understanding the mechanisms and spread of antimicrobial resistance. We discuss how this knowledge, coupled with ML- and AI-based approaches, can inform the prediction of resistance and a precision-medicine strategy that targets pathogenic bacteria specifically, thereby limiting resistance evolution and collateral damage to the microbiome. These accurate predictions of bacterial vulnerabilities will enable the adaptation of classical antimicrobial treatments with adjuvants, as well as the use of novel, narrow-spectrum therapeutics. Implementing these strategies, while also identifying key challenges, will help bring this strategy into clinical practice.
    Keywords:  antimicrobial resistance; artificial intelligence; evolution; machine learning; narrow-spectrum therapy; precision medicine
    DOI:  https://doi.org/10.1016/j.chom.2026.05.031
  36. Animals (Basel). 2026 Jun 16. pii: 1860. [Epub ahead of print]16(12):
      Bovine endometritis remains one of the most significant postpartum uterine disorders. It impairs uterine recovery, compromises fertility, and causes substantial economic losses in dairy production. Growing evidence suggests that the disease cannot be attributed solely to postpartum bacterial contamination; rather, it should be understood as a multifactorial failure to restore uterine homeostasis after calving. This review summarises the latest research findings on six interconnected aspects: the clinical significance of postpartum uterine disease; the diagnostic and biological differences between clinical and subclinical endometritis; the role of microbes in the uterus in health and disease; interactions between the host and uterine bacteria; the mechanisms of persistent inflammatory regulation; and current as well as emerging treatment strategies. Current evidence indicates that postpartum uterine disease is more strongly associated with dysbiosis, reduced microbial diversity, and disturbed microbial succession than with the presence of any single pathogen. Disease progression is driven by complex interplay among microbial ligands, epithelial and stromal immune responses, virulence-associated tissue injury, endocrine disruption, and impaired inflammatory resolution. Furthermore, persistent uterine inflammation is regulated by multilayered networks involving cytokines, prostaglandins, noncoding RNAs, extracellular vesicles, metabolic remodeling, and oxidative stress. Although conventional therapies remain relevant in certain clinical cases, microbiota-oriented approaches, particularly probiotic interventions, have emerged as promising adjunctive strategies for the prevention and control of the condition. Overall, bovine endometritis should be viewed as a disorder caused by disrupted interactions between the host, microbiota and inflammation. Future progress will depend on longitudinal, strain-resolved, and function-oriented studies to enable more precise and less antimicrobial-dependent interventions for postpartum uterine health.
    Keywords:  dairy cow; dysbiosis; endometritis; inflammatory persistence; innate immunity; postpartum disease; uterine microbiota
    DOI:  https://doi.org/10.3390/ani16121860
  37. Int J Microbiol. 2026 ;2026 6286424
       Background: Multidrug-resistant (MDR) infections represent a major challenge in surgical patients, particularly in settings with prolonged hospitalization and intensive care exposure. Identifying risk factors and their impact on mortality is essential for optimizing antimicrobial stewardship and infection control strategies.
    Methods: We conducted a retrospective observational study including surgical patients admitted to a Romanian tertiary-care hospital between 2020 and 2022. Demographic, clinical, microbiological, and antibiotic utilization data were analyzed using multivariate logistic regression and receiver operating characteristic (ROC) curve analysis to identify factors associated with MDR infection and in-hospital mortality.
    Results: Prolonged intensive care unit (ICU) stay and longer hospitalization were the main independent predictors of MDR infection. Antibiotic prophylaxis was also associated with MDR status, likely reflecting increased antimicrobial exposure in high-risk patients, while a higher comorbidity burden showed an inverse association. MDR infections were strongly associated with increased in-hospital mortality and remained an independent predictor after adjustment, alongside ICU stay and older age. MDR cases were characterized by more frequent use of broad-spectrum antibiotics, whereas non-MDR patients more commonly received narrower-spectrum regimens. The most frequent MDR pathogens included Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii.
    Conclusions: MDR infections in surgical patients are primarily driven by prolonged healthcare exposure, particularly ICU admission and extended hospitalization. These findings highlight the importance of targeted infection control measures and optimized antimicrobial use to reduce mortality and limit the spread of resistance.
    Keywords:  COVID-19; ICU stay; Romania; antibiotic prophylaxis; multidrug resistance; risk factors; surgical infections
    DOI:  https://doi.org/10.1155/ijm/6286424
  38. Acta Odontol Scand. 2026 Jun 26. 85 360-372
       OBJECTIVE: Although links exist between periodontitis and rheumatoid arthritis (RA), and the gut microbiome has been implicated in RA pathogenesis, the role of oral microbiome diversity in RA remains insufficiently characterized. This study aimed to explore the association between oral microbiome diversity (including alpha and beta diversity) and RA status through a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES).
    MATERIAL AND METHODS: This cross-sectional study analyzed data from 1,544 participants aged ≥ 20 years derived from the 2009-2012 NHANES cycles. We employed multivariate logistic regression, restricted cubic splines (RCS), receiver operating characteristic (ROC) curve analysis, SHapley Additive exPlanations (SHAP) method and beta diversity assessment (Principal Coordinate Analysis [PCoA] and Permutational Multivariate Analysis of Variance [PERMANOVA]) to examine associations between oral microbiome diversity metrics and RA.
    RESULTS: After adjustments, four alpha diversity metrics (observed amplicon sequence variants [ASVs]: OR [95% CI] = 0.996 [0.992, 0.999], P = 0.043; Faith's PD: OR [95% CI] = 0.943 [0.900, 0.988], P = 0.014; Shannon-Wiener index: OR [95% CI] = 0.786 [0.641, 0.965], P = 0.021; Simpson index: OR [95% CI] = 0.127 [0.018, 0.915], P = 0.037) were significantly inversely associated with the presence of RA. This relationship was approximately linear (P for nonlinear > 0.05) and moderated by socioeconomic factors (P for interaction < 0.05). ROC and SHAP analyses revealed that the Simpson index had the highest explanatory capacity for RA. However, beta diversity (Bray-Curtis, UniFrac distances) revealed no significant differences between RA and non-RA groups (all P > 0.05).
    CONCLUSIONS: Higher oral microbiome alpha diversity is significantly associated with lower prevalence of RA. Oral microbial diversity may serve as a potential indicator associated with RA status. However, given the cross-sectional nature of this study, longitudinal and interventional studies are warranted to further elucidate causal relationships.
    DOI:  https://doi.org/10.2340/aos.v85.46064
  39. Biofilm. 2026 Dec;12 100375
      Achromobacter xylosoxidans is an opportunistic pathogen in both cystic fibrosis (CF) and non-CF patients, in whom biofilm formation contributes to bacterial persistence and antibiotic tolerance. This study aimed to characterize early and mature biofilm formation in 57 clinical A. xylosoxidans isolates using complementary and physiologically relevant approaches and to compare biofilm phenotypes according to isolate origin (CF/non-CF). Early adhesion was assessed using the Biofilm Ring Test®, mature biofilm viable biomass was quantified under static conditions by colony-forming units counts, and biofilm dynamics were analyzed in a continuous-flow microfluidic system. The effects of five clinically relevant antibiotics (trimethoprim-sulfamethoxazole, piperacillin-tazobactam, meropenem, imipenem, and cefiderocol) were evaluated under dynamic conditions at sub-inhibitory concentrations (0.5 × Minimum Inhibitory Concentration (MIC)) and on preformed biofilm at inhibitory concentrations (10 × MIC). Non-CF isolates displayed faster early adhesion than CF isolates, whereas mature biofilm biomass was comparable between groups. If early adhesion did not predict mature biofilm biomass, dynamic biofilm coverage under flow conditions correlated with static mature biofilm levels. Sub-inhibitory antibiotic concentrations failed to prevent initial adhesion and elicited three distinct responses: biofilm formation enhancement (piperacillin-tazobactam, meropenem, imipenem), no effect (trimethoprim-sulfamethoxazole), or biofilm reduction (cefiderocol). Exposing mature biofilm to 10 × MIC identified trimethoprim-sulfamethoxazole and cefiderocol as the most effective agents in biofilm biomass reduction, whereas carbapenems and piperacillin-tazobactam were less effective. These findings provide new insights into A. xylosoxidans biofilm biology and may help guide therapeutic strategies for infections caused by this emerging, increasingly drug-resistant pathogen.
    Keywords:  Achromobacter xylosoxidans; Antibiofilm; Antibiotic; Biofilm; Cystic fibrosis; Early adhesion; Microfluidic flow system
    DOI:  https://doi.org/10.1016/j.bioflm.2026.100375
  40. Clin Exp Med. 2026 Jun 24.
      The occurrence and progression of autoimmune diseases (AIDs) result from the combined effects of genetic susceptibility, immune response defects, and environmental triggers. Among these, microorganisms, as key environmental factors, have been widely hypothesized to play a role in initiating AIDs, but the exact causal relationship remains to be demonstrated. This review aims to deeply explore the core role of specific microbial infections in triggering AIDs by integrating evidence from three dimensions: epidemiological investigations, clinical studies, and animal model research. We focused on analyzing nine AIDs, including Guillain-Barré syndrome, systemic lupus erythematosus, and rheumatoid arthritis, and confirmed that specific pathogens such as Campylobacter jejuni, Epstein-Barr virus, and Porphyromonas gingivalis can induce corresponding autoimmune pathological damage in susceptible individuals through mechanisms including molecular mimicry and bystander activation. Nevertheless, the field still faces important gaps that caused the chain from mechanism association to clinical application to break.This review integrates existing evidence and demonstrates that microbial infections are one of the important triggers for AIDS. It provides a new theoretical basis and direction for mechanistic research, risk early warning, and targeted intervention of related diseases.
    Keywords:  Autoimmune diseases; Infections; Initiating factors; Microorganisms; Pathogenesis
    DOI:  https://doi.org/10.1007/s10238-026-02206-3
  41. FEMS Microbiol Ecol. 2026 Jun 18. pii: fiag058. [Epub ahead of print]102(7):
      Research on the respiratory microbiome has moved beyond the sterile-lung paradigm, but disease-associated microbial patterns are still often described as static signatures. In this mini-review, we synthesize current evidence within a dynamic state-transition framework in which respiratory microbial communities are shaped by microbial immigration, elimination, local growth conditions, and host inflammatory tone. This framework traces the respiratory microbiome from early-life assembly and homeostatic maintenance to perturbation, recovery, or persistence in alternative ecological states. We discuss how barrier integrity, mucociliary clearance, mucus and nutrient landscapes, inflammatory feedback, microbial metabolites, and the gut-lung axis regulate microbial stability and disease susceptibility. Across asthma, chronic obstructive pulmonary disease, cystic fibrosis, bronchiectasis, and respiratory infection, dysbiosis is interpreted not as a set of disease-specific taxa, but as a context-dependent outcome of shared ecological mechanisms. We also highlight methodological and translational priorities, including contamination control in low-biomass samples, longitudinal sampling, multi-omics integration, spatial host profiling, and cautious interpretation of association versus causality. Viewing the respiratory microbiome as an ecological system in motion may better connect microbial dynamics with disease heterogeneity, risk stratification, and future microbiome-directed interventions.
    Keywords:  airway ecology; dysbiosis; gut–lung axis; immune regulation; multi-omics; respiratory microbiome
    DOI:  https://doi.org/10.1093/femsec/fiag058
  42. Front Dent Med. 2026 ;7 1864810
      Oral diseases represent one of the most widespread global health burdens, affecting billions of people worldwide, causing pain, disability, and substantial treatment costs. Despite their prevalence, progress in prevention and therapy has been limited, in part, by experimental models that do not fully capture the complexity of the oral biological and environmental landscape. Over the past decade, however, major advances in model development have expanded the possibilities for studying oral disease. This mini-review summarizes advances from 2015 to 2025, focusing on caries and endodontic infections, gingivitis and periodontitis, peri-implantitis, mucosal disorders, oral and oropharyngeal cancers, and salivary gland diseases. Recent innovations include saliva-derived biofilm systems that reproduce ecological transitions, organ-on-chip systems that replicate fluid dynamics, and patient-derived organoids and xenografts that preserve clinical characteristics. In parallel, immune-integrated models now allow direct interrogation of host responses to pathogens. Separate from these experimental platforms, advanced analytical and computational approaches, including single-cell profiling, spatial transcriptomics, radiomics, and artificial intelligence (AI)-assisted image analysis, are increasingly linking molecular signatures with structural and functional disease outcomes. Together, these experimental models and complementary analytical tools mark a shift from reductionist approaches toward dynamic, patient-relevant frameworks that better capture the complexity of oral diseases. Remaining challenges include modeling chronic disease progression, incorporating viral and autoimmune components, and improving reproducibility through standardization across platforms. Addressing these limitations will be important for translating next-generation experimental models into clinically meaningful advances in oral health care.
    Keywords:  artificial intelligence; epithelial-immune crosstalk; multispecies biofilms; oral disease models; organ-on-chip; patient-derived organoids; precision medicine; translational research
    DOI:  https://doi.org/10.3389/fdmed.2026.1864810
  43. J Clin Med. 2026 Jun 06. pii: 4402. [Epub ahead of print]15(12):
      Background: Full-mouth disinfection (FMD) has been proposed as an effective non-surgical approach for the management of periodontitis; however, its clinical and microbiological outcomes in patients with depressive comorbidity remain insufficiently explored. Methods: This prospective study included 80 patients diagnosed with stage II periodontitis, allocated into two groups based on the presence or absence of depressive disorder. All participants underwent standardized FMD. Clinical parameters, including bleeding on probing and plaque index, together with subgingival bacterial load (total bacterial load, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia), were assessed at baseline and 12 weeks post-treatment using quantitative polymerase chain reaction. Microbiological data were log10-transformed prior to statistical analysis. Results: Significant reductions in both clinical and microbiological parameters were observed following treatment in both groups. Improvements in bleeding on probing and plaque index were accompanied by a marked decrease in total bacterial load and in the targeted periodontal pathogens. Patients with depressive disorder exhibited a higher baseline microbial burden; however, post-treatment reductions were comparable between groups. Moderate positive correlations were identified between total bacterial load and clinical parameters. Conclusions: FMD was associated with substantial short-term improvements in both clinical and microbiological outcomes in patients with stage II periodontitis. Depressive comorbidity did not appear to adversely influence treatment response. These findings support the role of biofilm control as a central component of periodontal therapy across different patient profiles.
    Keywords:  Porphyromonas gingivalis; Treponema denticola; depression; full-mouth disinfection; periodontitis; real-time PCR; subgingival microbiota
    DOI:  https://doi.org/10.3390/jcm15124402
  44. Nurs Older People. 2026 Jun 24.
      Pressure ulcers are a frequent complication in hospitalised older adults and require expert nursing interventions to address the multiple factors involved. The aim of this scoping review was to map the nursing interventions that facilitate pressure ulcer healing in this patient group. The authors searched medical research databases and identified 15 relevant studies. The findings show that the pressure ulcer healing process in hospitalised older adults is complex and demands evidence-based nursing interventions supported by a multidisciplinary approach. Nurses' interventions should focus on nutritional support; repositioning, pressure redistribution and mobilisation; appropriate dressing selection; consideration of innovative treatments; and objective wound assessments and ongoing monitoring. Expert nursing care of pressure ulcers is essential to reduce complications, relieve pain and prevent infection, thereby reducing morbidity and improving older people's quality of life.
    Keywords:  clinical; gerontology; older people; pressure area care; pressure ulcers; skin; wound care; wound healing
    DOI:  https://doi.org/10.7748/nop.2026.e1550
  45. Acta Microbiol Immunol Hung. 2026 Jun 23. pii: 030.2026.03025. [Epub ahead of print]
      Multidrug-resistant (MDR) Gram-negative pathogens continue to threaten patient outcomes in intensive care units (ICUs) worldwide, particularly in regions where genomic surveillance is limited. Understanding intra-host genomic diversity and mobility of resistance determinants remain essential for mitigating global antimicrobial resistance (AMR) threats. Whole genome sequencing and molecular analysis were performed on three selected isolates to identify resistance and virulence determinants. The isolates exhibited complex and heterogenous resistomes shaped by extensive antimicrobial exposure during prolonged ICU care. Two genetically distinct Klebsiella pneumoniae strains (ST11 and ST15) demonstrating intra-patient strain diversity, an emerging trend in high-risk clinical settings globally, along with an Acinetobacter baumannii strain (ST944) were recovered from the same patient. Key resistance genes linked to mobile genetic elements (MGEs) were identified, including blaCTX-M-15 and blaNDM-5 in K. pneumoniae ST11 and blaADC-152 in A. baumannii. A plasmid-associated contig harbouring blaDHA-1 and qnr resistance genes represented a 'high-risk' mobile platform with international similarity in K. pneumoniae, highlighting the global circulation of resistance plasmids. Virulence profiling revealed conserved and unique determinants, including biofilm, siderophore, and secretion loci, with one isolate carrying a complete Yersiniabactin locus associated with MGEs. This study provides the first genome-resolved case from the Caribbean demonstrating intra-host co-existence of globally important MDR lineages and plasmid-mediated dissemination of key resistance genes. Within the global AMR challenge, this analysis offers novel insight into the convergence of resistance and virulence traits and highlights the value of localized genomic surveillance in understanding pathogen adaptation, mobility, and persistence under high antimicrobial pressure. These findings emphasize the importance of incorporating genomic data from diverse geographic regions into global AMR networks to better manage MDR ESKAPE pathogens in ICU environments.
    Keywords:  Acinetobacter baumannii; ESKAPE pathogens; Klebsiella pneumoniae; resistance; virulence
    DOI:  https://doi.org/10.1556/030.2026.03025
  46. Am J Health Syst Pharm. 2026 Jun 23. pii: zxag188. [Epub ahead of print]
       PURPOSE: To evaluate the impact of a multidisciplinary antimicrobial stewardship program (mASP) on adherence to recommended antimicrobial therapy in neurosurgical units.
    METHODS: A quasi-experimental study was conducted in Thammasat University Hospital between May 2020 and June 2022. Our primary outcome was adherence to recommended antimicrobial therapy, and secondary outcomes included clinical improvement, 30-day infectious disease-related mortality, antimicrobial use, and incidence of infection with multidrug-resistant (MDR) pathogens.
    RESULTS: Overall, 688 antimicrobial orders were reviewed during the study. The most prescribed antimicrobial for empiric therapy was piperacillin/tazobactam (266/688, 39.9%), and the most common source of infection was the respiratory tract (321/688, 46.7%). The overall adherence rate to recommended antimicrobial therapy was higher in the mASP period (70.3% vs 62.5%; P = 0.029). The overall acceptance rate of mASP recommendations was 83.1%. Furthermore, the mean volumes of carbapenem (P = 0.005) and vancomycin (P = 0.045) use declined, while the trend of cefazolin use increased (coefficient, 26.88; 95% confidence interval, 13.53 to 40.24; P < 0.001) during the study period. The incidence of infections caused by MDR pathogens significantly declined (P = 0.012), especially for infections caused by carbapenem-resistant Acinetobacter baumannii (P = 0.043). There were no differences in the secondary outcomes, inclusive of the proportion of patients with clinical improvement and 30-day infectious disease-related mortality.
    CONCLUSION: Implementation of an mASP in neurosurgical units was associated with improved adherence to recommended antimicrobial therapy, reduced use of broad-spectrum antibiotics, and a decline in the incidence of infections with MDR pathogens.
    Keywords:  antimicrobial stewardship; clinical pharmacist; multidisciplinary team; neurosurgery
    DOI:  https://doi.org/10.1093/ajhp/zxag188
  47. Antibiotics (Basel). 2026 Jun 07. pii: 581. [Epub ahead of print]15(6):
      It is crucial to consider newer antibiotics with activity against anaerobes and Helicobacter pylori, given their healthcare importance, and the constantly growing antibiotic resistance/multidrug resistance, which complicates the therapy. The aim of this review was to emphasize certain recently approved or still-under-investigation antibiotics with potential benefits for treating Clostridioides difficile infections (CDIs), other anaerobic infections, and those caused by H. pylori, covering recent data from articles published primarily in 2020-2026. Given the limited number of antibiotics for treating CDI and fidaxomicin nonavailability in many countries, it is necessary to conduct more extensive laboratory and clinical studies of promising antibiotics such as ibezapolstat, delafloxacin, lascufloxacin, omadacycline, eravacycline, ridinilazole, and CRS3123. Against Bacteroides fragilis group species, delafloxacin and eravacycline showed good activity. Research on rifasutenizol for bacterial vaginosis, sarecycline and nadifloxacin for acne vulgaris and amixicile for periodontal diseases needs to be expanded. For H. pylori infection, delafloxacin, sitafloxacin, nemonoxacin, zoliflodacin, and rifasutenizol may improve the suboptimal success of most eradication regimens. However, more efforts, in coordination between medical, scientific, manufacturing, and government representatives, should ensure wider access to and research on the newer antibacterials. Establishing more research groups, careful examination of market issues, and additional approaches, such as nanomaterials, efflux pump inhibitors, phage therapy, and CRISPR-Cas systems, should be beneficial. Notwithstanding the difficulties, there are many opportunities to promote research on and potential use of newer antibiotics which show advantages over the older antibacterials, and to make them available to numerous countries and patients worldwide.
    Keywords:  Clostridioides difficile; Helicobacter pylori; access; acne; activity; advantages; anaerobes; bacterial vaginosis; newer antibiotics; periodontal diseases
    DOI:  https://doi.org/10.3390/antibiotics15060581
  48. Ann Am Thorac Soc. 2026 Jun 20. pii: aaoag172. [Epub ahead of print]
      Since its identification in 2001, human metapneumovirus (hMPV) has been recognized as an important cause of acute respiratory tract infection in all age groups. Although infection is often mild in healthy adults, hMPV can cause severe lower respiratory tract disease, including pneumonia, in young children, older adults, individuals with chronic diseases and immunocompromising conditions, and residents of long-term care facilities. Accumulating evidence demonstrates that hMPV contributes substantially to hospitalization, intensive care unit admission, and mortality in these high-risk populations. Globally, hMPV circulates seasonally, most commonly in late winter and spring, contributing to both community- and healthcare-associated respiratory infections; however, the COVID-19 pandemic disrupted established epidemiology, resulting in shifts in epidemic timing, off-season resurgences, genotype replacement, and increased overlap with other respiratory viruses, while also providing insights into viral interference and multivirus cocirculation. Clinical manifestations of hMPV overlap with other respiratory viruses, including influenza virus or SARS-CoV-2, and selective diagnostic practices contribute to under-recognition and under-testing. Although no specific antiviral therapies or licensed vaccines are currently available, identification of hMPV has important implications for diagnostic accuracy, prognosis, antimicrobial stewardship, and infection prevention, particularly in hospital and long-term care settings. This review summarizes current evidence on the virology, epidemiology, post-COVID-19 trends, clinical manifestations, outcomes, diagnosis, and prevention of hMPV, with a particular focus on adults and other high-risk populations. We also review the current landscape of hMPV vaccine development and its potential implications for clinical practice and public health.
    Keywords:  human metapneumovirus; pneumonia; respiratory infection; respiratory virus
    DOI:  https://doi.org/10.1093/annalsats/aaoag172