bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2026–05–31
fifty-five papers selected by
Luca Bolliger, lxBio
  1. Cleaning and debridement in wound care: a review of wound infection management and the role of multidimensional dressings.
  2. Biofilm-Host Immune Crosstalk at the Diabetic Foot Ulcer Interface: Molecular Mechanisms, Immune Evasion, and Next-Generation Anti-Biofilm Strategies.
  3. Phage Therapy Beyond Static Pharmaceuticals: A Framework for Controlled Evolutionary Platforms.
  4. Viruses that heal: harnessing bacteriophages in the era of antibiotic resistance.
  5. Periodontitis and Rheumatoid Arthritis: Shared Pathophysiology, Bidirectional Association, and Therapeutic Implications-A Narrative Review.
  6. Isolation and Genomic Characterization of a Lytic Bacteriophage Against Multidrug-Resistant E. coli.
  7. Current Challenges and Potential Strategies to Enhance Efficacy of Oral Phage Therapy in Food Animals: A Systematic Review with Quantitative Analysis.
  8. Harnessing lytic phages for biofilm control in carbapenem-resistant Klebsiella pneumoniae causing urinary tract infection.
  9. Host-Pathogen Interactions in Cystic Fibrosis Lung Disease: Adaptation, Persistence, and Clinical Implications of Pseudomonas aeruginosa.
  10. A practical low-cost course module for teaching bacteriophage isolation to undergraduate students.
  11. Connecting the dots between phage pharmacokinetics, pharmacodynamics and immune interactions.
  12. Hydrogel-Based Platforms for Wound Care: Integrated Strategies for Antimicrobial Delivery and Biofilm Management.
  13. Phage-based microbiome manipulation reveals ecological interactions within gut communities.
  14. Isolation of Bacteriophages with Lytic Activity from Biological Samples of Left Ventricular Assist Device Patients: An In Vitro Study.
  15. The comparative review of hydrogel and hydrogel microneedle application for transdermal drug delivery.
  16. Fungal-Bacterial Interactions in Polymicrobial Infections: Hidden Threats.
  17. Microbial Dysbiosis in Photodermatoses: Formation, Pathogenesis and Intervention Strategies.
  18. The Role of Oral Pathobionts' Outer Membrane Vesicles in Cancer Pathology and Therapeutic Development.
  19. Phage Therapy in Combating Multidrug-Resistant Gram-Negative Pathogens: A Scoping Review.
  20. Unraveling Oral Dysbiosis: Microbial Complexity in Common Oral Diseases.
  21. The role of Veillonella species in oral carcinogenesis: is prevalence linked to oral squamous cell carcinoma?
  22. Quorum Sensing and Quorum Quenching in Pseudomonas aeruginosa and Staphylococcus aureus Infections: Therapeutic Potential, Limitations and Clinical Challenges.
  23. Development of the first European Xanthomonas euvesicatoria pv. euvesicatoria lytic bacteriophage cocktail effective in controlling bacterial spot disease in pepper plants.
  24. Sequential receptor engagement dictates the broad host range and fitness trade-offs of Salmonella phage PSA5-1.
  25. ESKAPE pathogens and antimicrobial resistance: emerging trends and therapeutic challenges.
  26. Activity of a three-phage combination against Mycobacterium tuberculosis in disease-relevant conditions.
  27. Cellulose-Based Hydrogels for Chronic Wound Healing: Bridging Biomaterial Design and Clinical Unmet Needs.
  28. Human antibodies as emerging drugs for antimicrobial resistance.
  29. Isolation, genomic characterization, and biofilm eradication activity of vB_PaP_DMTU_1, a novel lytic bacteriophage against Pseudomonas aeruginosa.
  30. Pathogenicity of P. gingivalis strains carrying clusters of specific polymorphic variants of peptidylarginine deiminase gene.
  31. Periodontitis, Endothelial Dysfunction, and Systemic Inflammation: A Systematic Review and Meta-Analysis of Flow-Mediated Dilation.
  32. The role of phages in plant-associated microbial communities.
  33. Association between oral microbial diversity and periodontitis in a nationally representative U.S. population: A cross-sectional study.
  34. Phage Φ170 biocontrol of multidrug-resistant Vibrio parahaemolyticus in a zebrafish model.
  35. Self-Powered Piezoelectric Nanofibrous Hydrogel for Synergistic Electro-Pharmacological Therapy of Chronic Wounds.
  36. CRISPR-Cas systems as next-generation antimicrobials: a systemic review of mechanisms, delivery strategies, and translational challenges.
  37. Reducing the impact of diabetic foot ulcers (REDUCE): study protocol for an effectiveness and cost-effectiveness randomised controlled trial with embedded process evaluation.
  38. Osteomyelitis.
  39. Association Between Diabetic Foot Lesions and Diabetic Foot Ulcers: A Cross-Sectional Study.
  40. Artificial intelligence for coordinating vaccine design, antiviral discovery, and real-world monitoring in the era of emerging and endemic viral threats.
  41. From Virtual Molecules to Clinical Trials: How AI Is Reshaping Preclinical Drug Discovery.
  42. Natural Compound-Loaded PLGA Nanocarriers for Infected Wound Management: A Review.
  43. Sepsis in end-stage liver disease and acute-on-chronic liver failure: pathophysiology, diagnostic challenges, and pharmacological management.
  44. The Diagnostic Complexities of Cystic Fibrosis: When to Think of It and What to Do?
  45. Intervening at the microbial crossroads: targeting inflammation across the oral-gut-reproductive microbiome crosstalk in atherosclerosis.
  46. Alveolar dysregulation of host response in pneumonia and ARDS: implications for immune modulation and infection.
  47. The Gut-Oral-Skin-Heart Microbiota Axis and Oxidative Stress: Where Have We Been and Where Are We Going.
  48. Neonatal Infections Caused by Multidrug-Resistant Bacteria: An Analysis of Prevalence, Risk Factors, and Therapeutic Implications-A Narrative Review.
  49. Disruptive innovation in antibiotic development: a vision for lysins.
  50. Counting to two: how phages decide between lysis and lysogeny.
  51. Physiotherapy Intervention for Diabetic Foot Ulcers: A Scoping Review.
  52. Optimizing antimicrobial stewardship in urology: a qualitative study on needs, values and requirements for clinical decision support.
  53. Differential Evolution of Achromobacter spp. Isolates in Upper and Lower Airways of People with Cystic Fibrosis.
  54. Molecular Methods to Detect Vibrio cholerae and Associated Bacteriophages among Diarrheal Patients in Bangladesh.
  55. Root Cause Analysis for Outbreaks of Carbapenem-Resistant Acinetobacter baumannii and Pseudomonas aeruginosa in a Pediatric Intensive Care Unit: A Retrospective Study.
  1. Br J Community Nurs. 2026 Jun;31(Sup6): S22-S28
    Cleaning and debridement in wound care: a review of wound infection management and the role of multidimensional dressings.
    Valerie Edwards-Jones.
      Following injury, most wounds resolve without any complication. However, if healing is impeded then the wound can become chronic and persist in a non-healing state for months, and even years in some cases. Globally, the majority of chronic wounds have biofilm present that does not resolve unless disrupted. Slough and devitalised tissue need to be removed as they act as a nidus for the biofilm. This article summarises the current methods available for cleaning and debridement and discusses topical antimicrobial treatments used to reduce bioburden.
    Keywords:  antimicrobial; bioburden; biofilm; chronic wounds; debridement; slough
    DOI:  https://doi.org/10.12968/bjcn.2025.0243
  2. Diabetes Metab Syndr Obes. 2026 ;19 608789
    Biofilm-Host Immune Crosstalk at the Diabetic Foot Ulcer Interface: Molecular Mechanisms, Immune Evasion, and Next-Generation Anti-Biofilm Strategies.
    Yu Han, Ye Yang.
      Diabetic foot ulcers (DFUs) are chronic wounds in which microbial persistence and defective host defense interact to impair healing. This review examines DFU through the biofilm-host immune interface rather than viewing biofilm as a purely microbiological problem. We summarize how the diabetic wound milieu, including hyperglycemia, impaired perfusion, neuropathy, and polymicrobial community structure, favors persistent biofilm infection, and how DFU-relevant biofilms evade clearance through matrix shielding, altered innate recognition, virulence-associated host modulation, and intracellular Staphylococcus aureus persistence. We further highlight two major immune-dysregulation axes: excessive neutrophil extracellular trap formation with NLRP3-centered inflammatory amplification, and perforin-2 suppression linked to AIM2-mediated pyroptotic injury. We also appraise emerging immune-aware antibiofilm strategies, particularly quorum-sensing interference, enzymatic matrix disruption, phage therapy, and selected immune-directed interventions. Overall, current evidence supports a model in which non-healing DFU reflects failed host-pathogen resolution at the biofilm-immune interface, with important implications for mechanism-guided therapeutic development.
    Keywords:  biofilm; diabetic foot ulcer; immune evasion; inflammasome; innate immunity; neutrophil extracellular traps; phage therapy; pyroptosis; quorum sensing
    DOI:  https://doi.org/10.2147/DMSO.S608789
  3. Viruses. 2026 May 01. pii: 534. [Epub ahead of print]18(5):
    Phage Therapy Beyond Static Pharmaceuticals: A Framework for Controlled Evolutionary Platforms.
    Hidetomo Iwano, Jumpei Fujiki, Tomohiro Nakamura.
      Rising antimicrobial resistance has revived global interest in phage therapy, yet its transition to standard clinical practice remains slow. This challenge is not solely due to a lack of efficacy. Instead, we face a fundamental conceptual barrier caused by an "evaluation mismatch." Traditional regulations treat phages as static chemical molecules-like taking a "snapshot." However, biologically, phages are dynamic, evolving populations-more like a living "movie." In this review, we use Schrödinger's cat metaphor to explain this reality: phage variability is not a defect, but an essential feature. To bridge this gap, we propose a Controlled Evolutionary Platform. By distinguishing between a fixed "Safety Core" and a fluctuating "Adaptive Periphery," we can manage viral evolution rather than trying to stop it. Ultimately, to integrate phages into modern medicine, we must redefine "consistency": shifting our focus from preserving a fixed genetic sequence to ensuring the reliable performance of population dynamics.
    Keywords:  antimicrobial resistance; bacteriophage; controlled evolutionary platforms; evolutionary dynamics; phage therapy; population heterogeneity; regulatory science
    DOI:  https://doi.org/10.3390/v18050534
  4. Vopr Virusol. 2026 Apr 30. 71(2): 91-108
    Viruses that heal: harnessing bacteriophages in the era of antibiotic resistance.
    T A Awotundun, O J Samson, A A Olanbiwoninu.
      The global rise in antimicrobial resistance (AMR) poses an urgent threat to public health, and novel alternatives to traditional antibiotics are needed. One of the most promising options is bacteriophages, viruses that infect and destroy bacteria. Once overshadowed by the discovery of antibiotics, phage therapy is now regaining attention, driven by advances in genomics, synthetic biology, and targeted medicine. This review examines the biology, diversity, and therapeutic use of bacteriophages in treating bacterial infections, especially those caused by multidrug-resistant pathogens. It also discusses how phages act through natural mechanisms, such as lytic enzymes (holins, endolysins, and muralysins), and highlights new genetic engineering techniques, such as CRISPR-Cas systems, phage recombineering, and synthetic genome reboots. In addition to clinical applications, we evaluate phages as biocontrol agents for food safety, environmental sanitation, and biofilm management. Additionally, the article explores key issues in phage therapy, including regulatory frameworks, formulation stability, dynamics of phage-host resistance, and the importance of rapid diagnosis. When properly integrated into modern health and biotechnology practices, bacteriophages offer significant potential and a sustainable solution to the global challenge of antimicrobial resistance.
    Keywords:  antibiotic resistance; bacteriophage; genetic engineering; infection control; phage therapy
    DOI:  https://doi.org/10.36233/0507-4088-366
  5. Healthcare (Basel). 2026 May 20. pii: 1411. [Epub ahead of print]14(10):
    Periodontitis and Rheumatoid Arthritis: Shared Pathophysiology, Bidirectional Association, and Therapeutic Implications-A Narrative Review.
    Neda Najafimakhsoos, Emanuela Pashollari, Nazzarena Malavolta, Francesca Zangari, Claudio Cesari.
      Periodontitis (PD) and rheumatoid arthritis (RA) are chronic inflammatory disorders that impose substantial individual and societal burdens worldwide. PD is characterized by progressive destruction of the periodontal ligament and alveolar bone, leading to tooth loss, impaired oral function, and sustained systemic inflammatory burden. RA, affecting approximately 0.5-1% of the population, is a chronic autoimmune disease marked by persistent synovial inflammation, progressive joint destruction, disability, and reduced quality of life. Increasing evidence indicates that these conditions are biologically and clinically interconnected. Both diseases share key pathogenic pathways, including microbial dysbiosis, immune dysregulation, chronic inflammation, genetic susceptibility, and aberrant autoantibody responses. Particular attention has focused on keystone periodontal pathogens such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, which may promote protein citrullination and the formation of anti-citrullinated protein antibodies (ACPA), thereby providing a plausible mechanistic bridge between periodontal infection and systemic autoimmunity. Shared genetic risk factors, including HLA-DRB1 susceptibility alleles, further support a common host predisposition. Clinical, epidemiological, and translational studies increasingly support a bidirectional association. Individuals with PD appear to have a higher risk of RA development, whereas patients with RA demonstrate greater prevalence, severity, and progression of periodontal disease. Interventional studies suggest that nonsurgical periodontal therapy may reduce local periodontal inflammation, circulating inflammatory biomarkers, and RA disease activity indices, while effective pharmacological control of RA may also improve periodontal outcomes. This narrative review critically evaluates the PD-RA relationship across four interconnected domains: (i) epidemiological and clinical associations between PD and RA, (ii) key mechanisms underlying RA pathogenesis, (iii) shared biological pathways linking both diseases, and (iv) the extent to which treatment of one condition influences the other. Particular emphasis is placed on major sources of heterogeneity and confounding-including smoking, metabolic comorbidities, disease stage, therapeutic exposure, and variable diagnostic definitions-that may explain inconsistencies across the literature. By integrating current mechanistic and clinical evidence, this review provides a structured synthesis that extends beyond a descriptive overview of association studies. A clearer understanding of the periodontal-rheumatologic axis may facilitate risk stratification, identify novel therapeutic targets, and support integrated multidisciplinary care. Targeting both oral and systemic inflammation may improve outcomes in patients with coexisting PD and RA and may potentially reduce the risk or severity of one condition in individuals already affected by the other.
    Keywords:  Porphyromonas gingivalis; anti-citrullinated protein antibodies; autoimmunity; bidirectional association; citrullination; disease-modifying antirheumatic drugs; microbial dysbiosis; oral microbiome; periodontal therapy; periodontitis; rheumatoid arthritis; systemic inflammation
    DOI:  https://doi.org/10.3390/healthcare14101411
  6. Viruses. 2026 Apr 30. pii: 532. [Epub ahead of print]18(5):
    Isolation and Genomic Characterization of a Lytic Bacteriophage Against Multidrug-Resistant E. coli.
    Ramesh Kumpatla, Vinaya Kruthi Vitala, Arunasree M Kalle.
      Antimicrobial resistance (AMR) has become a major concern in the treatment of bacterial infections, and bacteriophage therapy has emerged as a promising alternative to antibiotics. Bacteriophages are highly specific to their bacterial hosts; hence, isolating phages indigenous to a specific region offers a significant advantage against various pathogen strains. We have isolated a cocktail of bacteriophages against pathogenic E. coli from sewage water at a primary healthcare centre. Characterisation of the isolated phages demonstrated their stability across a broad pH and temperature range, strong lytic activity, and effective biofilm degradation, with no cross-reactivity with Staphylococcus aureus (S. aureus). Genomic analysis and phylogenetic studies indicated that the largest phage (by genome size) in the cocktail belongs to the genus Vequintavirus (myoviruses, rV5-like phages), and its genome sequence has been deposited in NCBI (Accession ID: PX741096). The phage genome was linear, with headful (PAC) packaging, encoded lysis proteins, and lacked antibiotic-resistant or major lysogeny-associated genes, collectively suggesting a lytic lifestyle. These findings emphasize the therapeutic potential of rV5-like phages and underscore the critical need to establish phage banks in India to improve disease management.
    Keywords:  bacteriophages; biofilm degradation; host-range specificity; lytic phages; multidrug-resistant E. coli; whole genome sequencing
    DOI:  https://doi.org/10.3390/v18050532
  7. Viruses. 2026 May 08. pii: 544. [Epub ahead of print]18(5):
    Current Challenges and Potential Strategies to Enhance Efficacy of Oral Phage Therapy in Food Animals: A Systematic Review with Quantitative Analysis.
    Md Ashiqur Rahman, Rebecca Abraham, David J Hampson, Sam Abraham, Jasim M Uddin.
      Phage therapy has enormous potential in combating bacterial resistance in food animals. However, its application via the oral route remains limited due to challenges associated with the gastrointestinal tract (GIT) environment and a lack of rigorous clinical trial evidence. Therefore, we systematically searched in Google Scholar, PubMed, Scopus, and Web of Science databases following PRISMA guidelines and finally identified 111 articles on oral phage therapy in food animals from where we summarized the key physiological and chemical factors of the gut environment hindering the effectiveness of oral phage therapy (OPT), examined the methods used to evaluate phage stability in the GI environment, and highlighted potential strategies to mitigate these challenges. In addition, we performed quantitative analysis to visualize in vitro pH and thermal stability patterns of phages targeting bacteria isolated from food animals and variability in buffer and incubation period across stability studies. The GIT consists of several anatomically and functionally distinct segments, where complex interactions occur among digestive enzymes, gastric acids, electrolytes, commensal microbiota, and mucosal immune components. The acidic pH of the stomach is a major barrier to successful oral phage delivery. According to our analysis of pH stability testing data from the reviewed studies, most phages targeting antimicrobial-resistant bacteria in food animals remained stable at pH 5-9 and inactivated under highly acidic (pH ≤ 2) or highly alkaline (pH ≥ 11) conditions. In addition, phages are susceptible to high temperatures (above 60 °C), digestive enzymes (e.g., pepsin, trypsin, lipases), bile salts, and host immune responses. Several in vitro laboratory techniques are available to assess phage stability under simulated GI conditions, but variations occur in the assessment protocols. Microencapsulation using alginate and chitosan has been used to protect phages from the adverse GI environment. Additionally, enteric-coated capsules, antacids, co-encapsulation with acid-neutralizing agents, consumption of alkaline water, and daily phage administration are suggested to improve phage survival and efficacy. For the successful clinical implementation of OPT in food animals, future research should focus on elucidating the molecular and physicochemical determinants of phage stability, understanding the humoral immune response to OPT, standardizing laboratory protocol for assessing phage viability, improving the scalability of encapsulation methods, and exploring other potential delivery techniques.
    Keywords:  GIT; food animals; microencapsulation; pH; phage therapy
    DOI:  https://doi.org/10.3390/v18050544
  8. Microbiol Spectr. 2026 May 29. e0339725
    Harnessing lytic phages for biofilm control in carbapenem-resistant Klebsiella pneumoniae causing urinary tract infection.
    Dipendra Kumar Mandal, Elisha Upadhyaya, Puja Dahal, Gaurav Adhikari, Rojina Pandey, Abdul Rehaman Miya, Sudip Timilsina, Pragya Sapkota, Shobha Amagain, David Pun, Kundan Khadka, Keshab Gorathoki, Bijita Neupane, Sangharsika Chaudhary, Sushila Thapa, Binod Khadka, Gun Raj Dhungana, Gorkha Raj Giri, Pragati Pradhan, Krishna Das Manandhar, Roshan Nepal, Rajindra Napit, Rajani Malla.
      Klebsiella pneumoniae is an opportunistic pathogen with rising multidrug resistance and biofilm-related infections. Molecular and phage characterization is crucial to understand resistance mechanisms and explore alternative therapies, such as phage therapy. Whole-genome sequencing and antibiotic susceptibility testing were performed on hospital-isolated K. pneumoniae (KP6697), followed by multilocus sequence typing (MLST), plasmid replicon analysis, and antimicrobial resistance gene (AMR) profiling using bioinformatics tools. Phages were isolated and characterized by electron microscopy, with assessments of anti-biofilm activity, lytic efficacy, stability, and host range. Phage genomes were sequenced to identify functional genes. The host K. pneumoniae (KP6697) was multidrug-resistant, exhibiting resistance to 18 of 22 tested antibiotics. Genome analysis identified it as sequence type 16 (ST16) with 8 plasmid replicons and 23 AMR genes, including blaCTX-M-15, blaNDM-5, and blaOXA-181. Functional annotations revealed extensive metabolic versatility and a rich repertoire of genes for biofilm formation, quorum sensing, secretion systems, and stress response. A lytic phage, Phage_KP6697_Omshanti, was isolated and classified as a Caudoviricetes member with a 45.3-kb genome encoding lysis, replication, and structural genes. The phage demonstrated short latency, high burst size, acceptable thermal and pH stability, and moderate host range against multiple CRKP and other bacterial isolates. Importantly, microscopy confirmed its ability to inhibit and degrade biofilms at multiple stages, highlighting its strong therapeutic potential. Lytic Phage_KP6697_Omshanti, with depolymerase and endolysin activity, isolated from carbapenem-resistant KP6697, showed high burst size, biofilm disruption, and had essential genomic traits suggesting its potential use as an anti-CRKP agent.IMPORTANCEKlebsiella pneumoniae is increasing multidrug resistance and robust biofilm formation pose severe clinical challenges, limiting treatment options. Understanding the molecular basis of its resistance and exploiting bacteriophages with strong biofilm-disrupting properties provide promising alternative therapeutic strategies. This study highlights the isolation and genomic characterization of a lytic phage with potent anti-biofilm activity against carbapenem-resistant K. pneumoniae, underscoring its potential in combating resistant infections.
    Keywords:  CRKP; bacteriophage; biofilm; multidrug resistance; phage therapy; quorum sensing
    DOI:  https://doi.org/10.1128/spectrum.03397-25
  9. Pathogens. 2026 May 21. pii: 557. [Epub ahead of print]15(5):
    Host-Pathogen Interactions in Cystic Fibrosis Lung Disease: Adaptation, Persistence, and Clinical Implications of Pseudomonas aeruginosa.
    Burcu Capraz Yavuz.
      Cystic fibrosis (CF) lung disease is characterized by chronic infection and progressive airway damage, driven by interactions between epithelial dysfunction, immune dysregulation, and microbial adaptation. Defective cystic fibrosis transmembrane conductance regulator (CFTR) function disrupts airway hydration and mucociliary clearance, creating a microenvironment that facilitates infection, particularly with Pseudomonas aeruginosa (P. aeruginosa). Within this environment, P. aeruginosa undergoes adaptive changes, including biofilm formation and metabolic reprogramming, which support long-term survival in the airway. Concurrently, host immune responses become dysregulated, with ineffective bacterial clearance and sustained neutrophil-dominated inflammation contributing to tissue injury. These processes establish a self-reinforcing cycle that drives disease progression. Importantly, early infection represents a critical therapeutic window during which bacterial populations remain more amenable to eradication before irreversible airway remodeling occurs. Delayed intervention promotes transition to a more treatment-refractory state and accelerates disease progression. Despite the clinical benefits of CFTR modulators, airway damage and established infections often remain. The relative contributions and interactions of epithelial dysfunction, immune dysregulation, and bacterial adaptation in sustaining chronic infection remain incompletely defined, representing a key knowledge gap. In this context, this review aims to integrate current evidence on host-pathogen co-adaptation in CF lung disease, with a particular focus on P. aeruginosa, and highlight emerging therapeutic strategies.
    Keywords:  Pseudomonas aeruginosa; bacteriophage therapy; chronic infection; cystic fibrosis; host–pathogen interactions
    DOI:  https://doi.org/10.3390/pathogens15050557
  10. J Microbiol Biol Educ. 2026 May 29. e0006526
    A practical low-cost course module for teaching bacteriophage isolation to undergraduate students.
    Luiz Felipe Leomil Coelho, Raíne Piva Amaral, Mateus de Souza Terceti, Ana Luisa Cauvila Dos Santos, Barbara Rafaela Ferreira Aio, Bianca Andrade de Carvalho, Luiz Cosme Cotta Malaquias, Gabriel Magno de Freitas Almeida.
      Bacteriophages are viruses that infect bacteria and have gained attention as promising tools against antimicrobial-resistant pathogens. Despite their relevance, phage biology remains underrepresented in undergraduate curricula. This study describes a low-cost course designed to introduce students to fundamental virology concepts through hands-on phage isolation, characterization, and genome analysis. Participants collected environmental water samples, performed phage enrichment, and detected viral plaques using the double-layer agar technique. The course also incorporated web-based bioinformatics activities using BLASTN and PhageScope, enabling students to explore genome size, GC content, gene annotation, and taxonomy without the need for coding knowledge or powerful computers. These activities strengthened the integration between laboratory and computational virology. Students had access to key concepts such as viral diversity, lytic cycles, biosafety, host specificity, and plaque quantification. This accessible educational model promotes active learning, democratizes access to virology training, and helps prepare future professionals for research in bacteriophage biology and phage therapy.
    Keywords:  bacteriophage; low-cost course; phage therapy
    DOI:  https://doi.org/10.1128/jmbe.00065-26
  11. Microb Pathog. 2026 May 25. pii: S0882-4010(26)00318-9. [Epub ahead of print]217 108592
    Connecting the dots between phage pharmacokinetics, pharmacodynamics and immune interactions.
    El-Sayed Khafagy, Azza A H Rajab, Ahmed Al Saqr, Wael A H Hegazy.
      Bacteriophage therapy is re-emerging as a promising strategy against multidrug-resistant bacterial infections, yet its clinical translation remains constrained by limited understanding of phage pharmacology and interactions within the human body. Unlike conventional antimicrobials, phages are self-amplifying biologically active particles that can interact with the immune system, such interactions can result in synergistic or antagonistic effects on immune function, leading to variable, unpredictable, and sometimes conflicting therapeutic outcomes. This review synthesizes the current knowledge based on in vivo findings related to phage pharmacokinetics and pharmacodynamics, especially regarding routes of administration, biodistribution, penetration through difficult-to-reach tissues, clearance pathways, and bacterial host effect. We further examine the current evidence for complex interplay between phages and mammalian immune system, including innate clearance, antibody-mediated neutralization, and the capacity of phages to induce immunological memory and immune tolerance. Current evidence indicates that the route and dose of phage administration can bias outcomes toward either tolerance or a robust neutralizing response, with important implications for repeated or prolonged therapy. Collectively, these insights emphasize the multifaceted aspects of phage therapy, which is not a straightforward therapeutic option, but inherently immunological and requires careful consideration of many factors prior to safe clinical application. Advancing the field toward rational, patient-specific application will require systematic human-based studies on pharmacokinetics and pharmacodynamics, longitudinal immune profiling, and rigorously designed clinical trials that directly link route, dose, formulation, and immune responses to reproducible clinical outcomes.
    Keywords:  Bacteriophage; Immune interactions; Phage therapy; Pharmacodynamics; Pharmacokinetics
    DOI:  https://doi.org/10.1016/j.micpath.2026.108592
  12. Gels. 2026 May 05. pii: 398. [Epub ahead of print]12(5):
    Hydrogel-Based Platforms for Wound Care: Integrated Strategies for Antimicrobial Delivery and Biofilm Management.
    Gabriela Marcelina Mihai, Liviu Martin, Lucretiu Radu, Madalina Aldea, Sorin Nicolae Dinescu, Andrei Gresita, Mihai Ruscu, Ramona Constantina Vasile, Alexandra-Daniela Rotaru-Zavaleanu.
      Chronic wounds, diabetic foot ulcers, venous leg ulcers, and pressure injuries affect millions of patients worldwide and cost healthcare systems in the order of $150 billion annually, yet treatment options have changed less than the scale of the problem would suggest. Biofilm formation, documented in up to 78% of chronic wounds, is a central cause: bacteria embedded in extracellular polymeric matrices tolerate antimicrobial concentrations up to 1000-fold higher than planktonic cells and sustain a chronic inflammatory state that actively prevents tissue repair. Hydrogels, crosslinked polymer networks with high water content and tunable physicochemical properties, have been widely studied as platforms for addressing these challenges, though the distance between laboratory results and clinical practice remains considerable. While recent reviews have summarized hydrogel materials or antimicrobial strategies in isolation, this review takes a different approach: we treat infection, biofilm persistence, and impaired regeneration as interconnected processes that must be addressed simultaneously, and we examine biofilm management as a distinct therapeutic target rather than merely a subset of antimicrobial delivery. We analyze hydrogel-based wound care across three integrated domains: design principles (natural, synthetic, and hybrid polymer systems; crosslinking strategies; and stimuli-responsive architectures), antimicrobial delivery (silver, antibiotics, antimicrobial peptides, natural agents, and controlled-release systems), and biofilm management (nanoparticle-mediated disruption, enzymatic EPS degradation, photodynamic approaches, quorum-sensing inhibition, and anti-adhesive surface engineering). For each area, we critically evaluate what the preclinical evidence supports, where it falls short, and what would be needed to bridge the gap to clinical application. Translation remains uneven. Among the many FDA- and EMA-cleared hydrogel dressings currently in clinical use, most are simple moisture-retaining or silver-containing formulations, while the multifunctional systems that dominate the research literature are at earlier stages of development. We discuss the main translational priorities, including more predictive preclinical models, long-term nanomaterial safety, harmonized outcome reporting, manufacturing scalability, and health economic evidence, as areas where further work can meaningfully accelerate clinical adoption.
    Keywords:  antimicrobial delivery; biofilm; chronic wounds; hydrogel wound dressings; nanocomposite hydrogels; stimuli-responsive biomaterials; tissue regeneration; wound healing
    DOI:  https://doi.org/10.3390/gels12050398
  13. bioRxiv. 2026 May 14. pii: 2026.05.13.724931. [Epub ahead of print]
    Phage-based microbiome manipulation reveals ecological interactions within gut communities.
    Taylor H Nguyen, Morgan Su, Nhien T Lu, Valentine Trotter, Saria A McKeithen-Mead, Jamie Alcira Lopez, Jiawei Sun, Zachary Hallberg, Handuo Shi, Po-Yi Ho, Brian C DeFelice, Michiko E Taga, Adam M Deutschbauer, Andrew J Hryckowian, Kerwyn Casey Huang.
      Mechanistic understanding of gut ecology is limited by the availability of tools for precise manipulation of microbiome composition. Here, we isolate lytic phages to enable targeted removal of gut commensal Escherichia fergusonii ( Ef ) from complex, undefined stool-derived in vitro communities. A single phage drove resistance without fitness cost in monoculture, but resistant Ef exhibited reduced fitness in communities, enabling expansion of closely related Proteobacteria. Resistance arose via reversible promoter inversion linked to outer-membrane function. A phage cocktail overcame resistance to achieve Ef knockout across communities with minimal collateral effects. Using knockout communities, we show that Ef is necessary and sufficient for preventing Salmonella invasion. Replacement with an Ef transposon-mutant library revealed that community-specific fitness defects are enriched in genes involved in outer-membrane assembly. Disruption of these genes sensitized Ef to antagonistic community members, highlighting interspecies warfare as a key driver of microbiome ecology. These results establish phage-mediated perturbation as a framework for linking species to community-level function and for enabling precision microbiome engineering.
    DOI:  https://doi.org/10.64898/2026.05.13.724931
  14. Viruses. 2026 Apr 30. pii: 526. [Epub ahead of print]18(5):
    Isolation of Bacteriophages with Lytic Activity from Biological Samples of Left Ventricular Assist Device Patients: An In Vitro Study.
    Balazs Sax, Adam Koppanyi, Katalin Kristof, Akos Kiraly, Gyula Prinz, Istvan Hartyanszky, Gergely Gyorgy Nagy, Istvan Nemet, Fanni Temesvari-Kis, Balazs Kiss, Bela Merkely.
      Percutaneous cable infection of left ventricular assist device (LVAD) patients is a significant source of morbidity, often caused by biofilm-producing or multidrug-resistant bacteria. We hypothesized that bacteriophage viruses can be identified from biological samples of patients with active driveline infection. Six patients with local percutaneous lead infections were enrolled. Microbiological samples were collected from the infected wound and other skin regions. The isolated viral strains and phages from wastewater samples were then tested against the pathogen bacterial cultures in vitro. Biofilm disruption assay and genetic analysis of the strains were also performed. Bacteriophages with lytic activity could be identified from samples of two patients. One patient contained four strains showing strong efficacy against his own Staphylococcus epidermidis. Furthermore, this bacterium was susceptible to phages identified from another patient and strains from wastewater samples. Genomic analysis suggested lysogenic lifestyle of the phages. However, none of them have shown any microbiological signs of lysogeny. In conclusion, we have been able to prove in vitro lytic activity of bacteriophages originating from the same LVAD patient. We also found effective phages in biological samples of other patients and wastewater samples, suggesting that patients implanted in the same center may share bacteriophage flora.
    Keywords:  bacteriophages; biofilms; driveline infection; left ventricular assist device; phage therapy
    DOI:  https://doi.org/10.3390/v18050526
  15. EPMA J. 2026 Jun;17(2): 457-477
    The comparative review of hydrogel and hydrogel microneedle application for transdermal drug delivery.
    Yan Zhang, Pengyuan Liu, Shaoyu Zhou, Baochun Li, Bingjie Cai, Jingan Li, Kun Zhang.
      Predictive, preventive, and personalized medicine (3PM) represents the optimal healthcare paradigm, innovative treatment approaches can significantly improve the management of chronic diseases. Hydrogel and hydrogel microneedles have emerged as a transformative platform for transdermal drug delivery. This review presents a comprehensive comparative analysis of hydrogels and hydrogel microneedles, focusing on their structure and morphology, preparation processes, mechanical properties, drug delivery methods, biosafety and degradation behaviors. It further underscores the distinct advantages and emerging applications of hydrogel microneedles including the drugs administration of Ciprofloxacin, Doxorubicin and Insulin, etc., as well as their use in transdermal drug delivery, vaccination, wound healing, tissue regeneration, and biosensing. The innovative merits of hydrogel microneedles are particularly evident in mitochondrial biosensing, digital health monitoring and personalized rehabilitation. These insights will facilitate the rational design and optimization of hydrogel-based microneedles, thereby advancing their application in biomedical therapies.
    Keywords:  Biosensing; Digital health monitoring; Drug administration; Hydrogel microneedles; Hydrogels; Predictive preventive personalized medicine (3PM); Tissue regeneration; Vaccination; Wound healing
    DOI:  https://doi.org/10.1007/s13167-026-00451-w
  16. Microbiologyopen. 2026 Jun;15(3): e70320
    Fungal-Bacterial Interactions in Polymicrobial Infections: Hidden Threats.
    Mohammad Javad Roustaye Gourabi, Masoud Kargar, Atefeh Kamali, Javad Yasbolaghi Sharahi.
      Polymicrobial infections involving fungi and bacteria represent a major and increasingly recognized clinical challenge, in which interkingdom interactions significantly amplify disease severity, antimicrobial resistance, and treatment failure. Rather than passive co-existence, fungal-bacterial communities form highly coordinated systems driven by physical adhesion, quorum sensing, metabolic interdependence, and biofilm-mediated structural reinforcement. These cooperative interactions, exemplified by pairs such as Candida albicans-Staphylococcus aureus and Pseudomonas aeruginosa-Aspergillus fumigatus, promote the development of treatment-recalcitrant biofilms with enhanced immune evasion and multidrug tolerance. The global rise of multidrug-resistant (MDR) and extensively drug-resistant (XDR) pathogens has further intensified this burden, with polymicrobial biofilms now representing a post-antibiotic clinical scenario in which therapeutic failure is driven not by individual resistant organisms but by emergent, cooperative resistance architectures. Conventional diagnostic approaches remain insufficient, as culture-based methods frequently fail to capture the complexity of mixed microbial communities. Emerging technologies such as MALDI-TOF mass spectrometry, metagenomic sequencing, and fluorescence in situ hybridization offer improved resolution but are not yet fully integrated into routine clinical practice. Therapeutically, increasing evidence indicates that monotherapy is inherently inadequate in polymicrobial infections due to the emergent nature of microbial cooperation. Effective management therefore requires combination strategies that simultaneously target multiple pathogens and their shared biofilm infrastructure. These include antibiotic-antifungal combinations, phage therapy, enzymatic and nanoparticle-mediated biofilm disruption, metabolic interference, and host-directed immunomodulation. Importantly, recent advances also highlight the role of biophysical properties such as biofilm viscoelasticity and matrix stiffness as critical and previously underappreciated therapeutic targets. This review uniquely integrates biochemical, biophysical, and therapeutic dimensions of polymicrobial infections into a unified systems-level framework in which microbial cooperation is the central driver of pathogenesis, resistance, and treatment failure. Fungal-bacterial interactions are thereby positioned along a dynamic continuum from commensalism to pathogenesis, shaped by host susceptibility and environmental perturbations. Future progress will depend on interdisciplinary strategies combining multi-omics technologies, precision diagnostics, and microbiome-informed therapeutic design to effectively disrupt these complex microbial networks.
    Keywords:  antimicrobial resistance; biofilm viscoelasticity; diagnostic Challenges; fungal‐bacterial interactions; mixed‐species biofilms; therapeutic strategies
    DOI:  https://doi.org/10.1002/mbo3.70320
  17. Curr Issues Mol Biol. 2026 May 09. pii: 493. [Epub ahead of print]48(5):
    Microbial Dysbiosis in Photodermatoses: Formation, Pathogenesis and Intervention Strategies.
    Lanhai Zhong, Tian Wang, Lu Tang, Jiande Han, Qun Zhao, Naiyu Lin.
      Recent studies have reported skin microbiome dysbiosis in patients with photodermatoses, featuring enriched Staphylococcus aureus colonization and decreased microbiome diversity. We propose that ultraviolet radiation (UVR), along with atypical antimicrobial peptides, may exert selective pressure on the skin microbiome, while cytokine dysregulation and a reduction in commensal bacteria amplify microbial dysbiosis. Dysbiotic microorganisms further release pathogen-associated patterns and virulence factors, and activate tissue-resident memory T cells, which collectively contribute to local inflammation. These mechanisms establish the skin microbiome as a potential target for early intervention. Potential therapeutic strategies may include antibiotics, phototherapy, bleach baths, phage therapy, and microbiota-based therapies. This review integrates current findings from microbial ecology, molecular biology, and host immunology to outline a conceptual framework linking UVR exposure, microbiome alterations, and cutaneous immune responses, while emphasizing the current limitations and evidence gaps in this field.
    Keywords:  Staphylococcus aureus; photodermatoses; skin microbiome; tissue-resident memory T cells; ultraviolet radiation
    DOI:  https://doi.org/10.3390/cimb48050493
  18. Cells. 2026 May 08. pii: 855. [Epub ahead of print]15(10):
    The Role of Oral Pathobionts' Outer Membrane Vesicles in Cancer Pathology and Therapeutic Development.
    Sara Hadjigol, Bansari A Shah, Negar Yazdani, Neil M O'Brien-Simpson.
      Cancer remains one of the leading causes of mortality worldwide, with increasing recognition of the host microbiome as a modifiable contributor to tumour initiation and progression. Among microbial mediators, outer membrane vesicles (OMVs) derived from Gram-negative oral pathobionts have emerged as critical effectors of host-microbe interactions. These nanoscale vesicles function as delivery systems for a diverse range of bioactive cargo, including virulence factors, lipopolysaccharides, proteins, and nucleic acids, enabling both local and systemic modulation of host cellular processes. Emerging evidence suggests that OMVs produced by oral pathobionts, particularly Porphyromonas gingivalis and Fusobacterium nucleatum, are associated with tumour-promoting inflammation, immune dysregulation, epithelial transformation, and metastatic progression. Mechanistically, OMVs have been shown to activate key signalling pathways, disrupt mitochondrial function, induce oxidative stress, and reprogram the tumour microenvironment in ways that favour cancer cell survival and immune evasion. In addition, OMV-mediated modulation of host responses has been linked to resistance to anticancer therapies. In this review, we synthesize current evidence on the role of oral pathobionts' OMVs in cancer biology, with a focus on their contributions to tumour initiation, progression, and metastasis. We further discuss emerging clinical associations, the potential of OMV-derived components as diagnostic biomarkers, and the growing interest in engineered OMVs as platforms for therapeutic intervention. Finally, we highlight key challenges and knowledge gaps that must be addressed to advance the translational application of OMV-based strategies in oncology. Overall, OMVs represent a promising but still evolving link between the oral microbiome and cancer, offering new insights into disease mechanisms and potential avenues for diagnosis and therapy.
    Keywords:  Fusobacterium nucleatum; Porphyromonas gingivalis; cancer; chemoresistance; inflammation; microbial biomarkers; oral microbiome; outer membrane vesicles
    DOI:  https://doi.org/10.3390/cells15100855
  19. Pharmaceuticals (Basel). 2026 May 03. pii: 727. [Epub ahead of print]19(5):
    Phage Therapy in Combating Multidrug-Resistant Gram-Negative Pathogens: A Scoping Review.
    Asif Sukri, Bruno Silvester Lopes, Alfizah Hanafiah.
      Background: The emergence of multidrug-resistant (MDR) Gram-negative pathogens, namely Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii and Helicobacter pylori, necessitates urgent therapeutic alternatives. This scoping review aimed to summarize the current evidence on the efficacy of lytic bacteriophages against these critical MDR pathogens, and to identify existing research gaps and implementation challenges. Methods: The literature search was conducted by searching PubMed, Web of Science, and Scopus AI for studies published from 2015 to 2025. The inclusion criteria focused on experimental and human studies evaluating phage therapy against MDR, extensively drug-resistant (XDR), or pan-drug-resistant (PDR) strains in the four target species. A total of 172 articles were included. Results: A number of studies showed an increasing trend (2015-2025), focusing mainly on K. pneumoniae (n = 65), P. aeruginosa (n = 55), and A. baumannii (n = 48). No eligible studies for MDR H. pylori were found. All 172 studies confirmed lytic activity, with phage cocktails showing superior antibacterial activity than single phages in four studies. Phages also demonstrated antibiofilm activity (n = 44). Most animal studies reported successful bacterial reduction in animals treated with phages, and 87.5% of 23 human case studies reported patient improvement or infection clearance. However, heterogeneity in the types of animal models used and in dosage and administration routes in human studies was notable. Conclusions: Lytic bacteriophages exhibit strong potential as a new therapeutic option. Key challenges include the lack of data for MDR H. pylori, heterogeneity in animal models, and a paucity of large-scale human clinical trials. Future research must prioritize standardization, mechanistic studies, and conducting robust human trials to enable clinical translation and regulatory acceptance.
    Keywords:  Acinetobacter baumannii; Helicobacter pylori; Klebsiella pneumoniae; Pseudomonas aeruginosa; multidrug resistance; phage therapy
    DOI:  https://doi.org/10.3390/ph19050727
  20. Microbiologyopen. 2026 Jun;15(3): e70305
    Unraveling Oral Dysbiosis: Microbial Complexity in Common Oral Diseases.
    Zixi Kang, Hong Huang, Jin Lin, Yanan Niu, Jiaxin Chen, Jiaxuan Tang, Zhengyuan Hu, Peng Liu, Jun Qu.
      The oral microbiome is highly intricate, hosting billions of bacteria and other microorganisms that form biofilms on various oral surfaces. An imbalanced ecological relationship between the microbial community and the host can lead to various oral diseases. This narrative review explores the current understanding of the correlation between the microbiome and oral diseases. The main body of this manuscript is divided into seven parts, including a review of current research on oral microbial colonization and early life development, an introduction to five common oral diseases related to microorganisms, and a discussion on the relationship between dental caries and periodontal disease at the microbial level. Our aim in presenting this review is to offer a valuable resource for further research on the role of oral microorganisms in diagnosing and treating oral diseases. The oral microbiome's significant impact and diversity characteristics on health and disease have been recognized; however, there remains a severe lack of systematic understanding of its functions, host interactions, and environmental factors. Comprehensive research is urgently needed to elucidate the mechanisms that maintain its ecological balance, providing a scientific foundation for the precise prevention and control of oral diseases. This review comprehensively synthesizes current knowledge regarding oral microbial dysbiosis in the context of the major oral diseases mentioned and proposes a conceptual framework grounded in microbial ecology to elucidate disease progression and guide therapeutic strategies.
    Keywords:  clinical implications; dysbiosis; microbiome; oral diseases; pathogenesis
    DOI:  https://doi.org/10.1002/mbo3.70305
  21. Front Oral Health. 2026 ;7 1740043
    The role of Veillonella species in oral carcinogenesis: is prevalence linked to oral squamous cell carcinoma?
    Citra Fragrantia Theodorea, Nadhira Aurynna Azzahra, Erik Idrus, Fahrul Nurkolis, Ariadna Adisattya Djais, Izumi Mashima.
      Oral squamous cell carcinoma (OSCC) remains a significant health challenge because of its aggressive nature and poor survival outcomes. While established risk factors such as tobacco use, alcohol consumption, and human papillomavirus play critical roles, increasing evidence suggests that oral microbial dysbiosis may contribute to carcinogenesis. Among oral commensals, Veillonella species have gained attention because of their ecological role in oral biofilms and metabolic interactions with other microbes, and have also been increasingly identified in altered abundances within OSCC patient samples. This narrative review synthesizes available clinical, epidemiological, and molecular studies investigating the prevalence and biological roles of Veillonella species in OSCC. Relevant English-language publications between 2000 and 2025 were identified through database searches in Pubmed Scopus and Web of Science using keywords related to Veillonella, oral microbiome, dysbiosis, and OSCC. The reviewed evidence reveals a dynamic and stage-dependent shift in Veillonella abundance during oral carcinogenesis. Several studies report enrichment of Veillonella in oral potentially malignant disorders and early tumorigenesis, whereas reduced levels are frequently observed in advanced OSCC. These findings suggest that Veillonella may function as an ecological modulator of tumor-associated microbiota rather than as a single pathogenic driver. Proposed mechanisms include metabolic cross-feeding with lactic-acid-producing bacteria, modulation of inflammatory pathways, biofilm restructuring, and host-microbe metabolic signaling. Overall, current evidence supports a microbial ecological shift model, in which Veillonella participates in early dysbiotic transitions preceding OSCC development but may decline as tumor microenvironments evolve. Further standardized and multiomics studies are needed to clarify its potential as a microbiome-based biomarker and therapeutic target.
    Keywords:  Veillonella species; biomarker; carcinogenesis; inflammation; oral dysbiosis; oral microbiome; oral squamous cell carcinoma (OSCC); therapeutic target
    DOI:  https://doi.org/10.3389/froh.2026.1740043
  22. Antibiotics (Basel). 2026 Apr 29. pii: 447. [Epub ahead of print]15(5):
    Quorum Sensing and Quorum Quenching in Pseudomonas aeruginosa and Staphylococcus aureus Infections: Therapeutic Potential, Limitations and Clinical Challenges.
    Emilia Nowak, Matylda Korgiel, Karolina Pawłuszkiewicz, Jarosław Widelski, Bachar Cheaib, Emil Paluch.
      Antimicrobial resistance (AMR) represents a major global health threat, largely driven by antibiotic overuse and the protective role of bacterial biofilms. Quorum sensing (QS), a bacterial communication system regulating virulence and biofilm formation, has emerged as a promising therapeutic target. Quorum quenching (QQ), which disrupts QS without directly inhibiting bacterial growth, is considered a potential anti-virulence strategy that may reduce selective pressure for resistance. This review critically evaluates recent advances in QQ research, focusing on its clinical applicability, limitations, and risks. We analyzed studies from the last five years involving natural compounds, synthetic molecules, nanoparticles (NPs), and combination therapies targeting key pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus in models of lung diseases, mainly cystic fibrosis, chronic wounds, burns, and implant-associated infections. While numerous compounds demonstrate significant in vitro anti-biofilm and anti-virulence activity, major challenges remain, including limited in vivo validation, pharmacokinetic constraints, toxicity concerns, microbiome disruption, and the potential development of tolerance or functional resistance. Although QQ offers a promising adjunctive approach to conventional antibiotics, its long-term clinical feasibility requires comprehensive evaluation of evolutionary dynamics, host-microbe interactions, and safety profiles.
    Keywords:  Pseudomonas aeruginosa; Quorum quenching; Quorum sensing; Staphylococcus aureus; anti-virulence therapy; biofilms; drug resistance; microbial
    DOI:  https://doi.org/10.3390/antibiotics15050447
  23. Front Microbiol. 2026 ;17 1821339
    Development of the first European Xanthomonas euvesicatoria pv. euvesicatoria lytic bacteriophage cocktail effective in controlling bacterial spot disease in pepper plants.
    Elena G Biosca, Isabel Salas-Lastres, José F Català-Senent, Félix Morán, Ana Palacio-Bielsa, Belén Álvarez.
      Bacterial spot of pepper and tomato is one of the most challenging xanthomonad diseases, affecting widely cultivated horticultural crops. Xanthomonas euvesicatoria pv. euvesicatoria (Xee), the main causal agent of bacterial spot in pepper, causes significant yield losses worldwide and is increasingly being reported in Southern Europe, including Spain, where outbreaks of bacterial spot have mainly been detected in pepper. Current management strategies mainly rely on copper-based compounds with limited efficacy due to the development of resistance and environmental and health concerns. Bacteriophages represent a promising safe and sustainable ecological alternative. In this study, lytic phages infecting Xee were isolated from pepper plots affected by bacterial spot disease in two distant regions of Spain. Genomic and taxonomic analysis of five selected phages classified them as belonging to the genus Beograduvirus and confirmed their lytic nature and safety. Three phages were investigated further because of their ability to infect multiple strains of the pathogen while remaining highly specific. These phages exhibited myovirus morphology and remained stable across temperatures and pH conditions relevant to field application. In vitro co-culture of the target bacteria with the three phages, either individually or in combination, revealed that the three combined phages controlled pathogen growth significantly better than single-phage treatments. In pepper plants, foliar application of the phage cocktail by dipping or spraying markedly reduced disease symptoms after inoculation with Xee, with spraying giving the most consistent results regardless of the bacterial strain tested. This is the first European phage cocktail that can effectively control Xee in pepper plants, highlighting its potential as a practical tool for the integrated management of this disease.
    Keywords:  Beograduvirus; One-Health; SDG; Xanthomonas euvesicatoria pv. euvesicatoria; bacterial spot; biocontrol; lytic phage cocktail; pepper
    DOI:  https://doi.org/10.3389/fmicb.2026.1821339
  24. Microbiol Spectr. 2026 May 29. e0024826
    Sequential receptor engagement dictates the broad host range and fitness trade-offs of Salmonella phage PSA5-1.
    Muhammad Saleem Iqbal Khan, Yuan Li, Shenlin Ji, Shuangshuang Hou, He Li, Yaoyuan Chang, Demeng Tan, Ju Wu, Jiajun Yin.
      The global rise of multidrug-resistant (MDR) Salmonella spp. necessitates the development of alternative antimicrobials, yet the molecular determinants of phage host range and the collateral effects of bacterial resistance remain poorly defined. Here, we characterize PSA5-1, a T4-like phage, and decipher the hierarchical two-step receptor recognition governing its infection of Salmonella enterica. We demonstrate that PSA5-1 utilizes the outer-membrane porin C (OmpC) as a primary receptor required for reversible adsorption, while the lipopolysaccharide (LPS) inner core is required for productive infection. Selection for PSA5-1 resistance reveals distinct evolutionary trajectories: whereas ompC deletion confers resistance with minimal fitness costs, disruption of the LPS core (via rfaF) triggers profound physiological remodeling and enhanced biofilm formation. Comparative genomics further indicates that host susceptibility is governed by OmpC sequence conservation and O-antigen diversity, with additional contributions from intracellular defense systems. By mapping the interplay between receptor engagement and resistance-associated trade-offs, our findings provide a mechanistic framework for the rational design of precision phage-based interventions against enteric pathogens.IMPORTANCEThe increasing prevalence of multidrug-resistant Salmonella spp. necessitates the development of precision antimicrobial alternatives to antibiotics, such as bacteriophage therapy. However, the successful clinical application of phages is often hampered by the rapid evolution of bacterial resistance and complex host defense mechanisms. In this study, we dissect the infection logic of the phage PSA5-1, identifying the outer-membrane protein C-lipopolysaccharide inner core dependency as a critical determinant enabling sequential receptor engagement during genome delivery. By mapping the genetic determinants of susceptibility, ranging from receptor variation to intracellular immunity, we highlight the evolutionary trade-offs Salmonella must navigate to evade infection. These findings provide a mechanistic blueprint for selecting phages that exploit conserved surface targets, ultimately aiding in the design of therapeutic cocktails that are robust against bacterial resistance.
    Keywords:  Salmonella enterica; bacteriophage; phage receptors; phage–host interaction
    DOI:  https://doi.org/10.1128/spectrum.00248-26
  25. Future Microbiol. 2026 May 25. 1-15
    ESKAPE pathogens and antimicrobial resistance: emerging trends and therapeutic challenges.
    Jun An Low, Jia Suen Pang, Timothy Chen Ming Lim, Sivachandran Parimannan, Heera Rajandas, Candy Chuah.
      Antimicrobial resistance (AMR) has emerged as one of the most-pressing global health threats of the 21st century, compromising the efficacy of existing antibiotics and threatening modern medical practices. Among the most-concerning multidrug-resistant (MDR) pathogens are the ESKAPE organisms (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.), which the World Health Organization (WHO) has designated as a high-priority group due to their capacity to evade conventional antibiotics and cause severe hospital-acquired infections (HAIs). Infections caused by ESKAPE pathogens are notoriously difficult to treat, frequently associated with poor clinical outcomes, high morbidity, and significant mortality, particularly in immunocompromised individuals. This review provides a comprehensive overview of ESKAPE pathogens, focusing on their clinical relevance, virulence determinants, diverse antibiotic resistance mechanisms and potential future therapeutic approaches. Furthermore, it highlights the recent global prevalence data from 2021 to 2025, demonstrating the escalating burden of MDR ESKAPE infections. Collectively, these insights reinforce the urgent need for enhanced surveillance, stringent infection control measures, and the development of innovative therapeutic strategies to address the growing threat of ESKAPE-driven AMR.
    Keywords:  Antimicrobial resistance (AMR); ESKAPE pathogen; antibiotic; hospital-acquired infection (HAI); multidrug-resistant (MDR) pathogen; vaccine
    DOI:  https://doi.org/10.1080/17460913.2026.2677420
  26. bioRxiv. 2026 May 11. pii: 2026.05.11.724220. [Epub ahead of print]
    Activity of a three-phage combination against Mycobacterium tuberculosis in disease-relevant conditions.
    S Janssen, S E Larsen, M Pozuelo Torres, M Beldjenna, C A Guerrero Bustamante, I Florian, T Smytheman, T Guo, R C van Wijk, G F Hatfull, A H Diacon, R N Coler, J van Ingen.
      Phage therapy offers promise to combat antimicrobial resistance, including drug-resistant tuberculosis (TB). Understanding phage activity against Mycobacterium tuberculosis (Mtb) adapted to physiologic microenvironments, such as hypoxia and acidity in granulomas, is essential since these conditions induce non-replicating states. We evaluated a phage combination against Mtb under hypoxic, acidic (pH 5.5), and stationary-phase conditions in vitro . In planktonic Mtb growth conditions, phage concentrations increased around day seven followed by a significant reduction in Mtb H37Rv load, which was maintained over 31 days. Phage addition prevented regrowth was observed with rifampicin and isoniazid alone. Individual phage stability was differentially affected by acidic media conditions, resulting in variability of antimycobacterial activity. In hypoxic conditions and stationary growth experiments, phage titers remained stable over time with no change in mycobacterial load compared to controls. Model-based predictions were able to adequately capture phage-mycobacterial interactions with and without rifampicin. The lack of antimycobacterial activity in assays with non-replicating mycobacteria suggest that phages need actively replicating mycobacteria to exert lytic activity. Stable phage concentrations in assays with non-replicating mycobacteria suggests low grade phage replication in these conditions. Established models can support future study design through simulations of different experimental scenarios.
    DOI:  https://doi.org/10.64898/2026.05.11.724220
  27. Gels. 2026 May 08. pii: 410. [Epub ahead of print]12(5):
    Cellulose-Based Hydrogels for Chronic Wound Healing: Bridging Biomaterial Design and Clinical Unmet Needs.
    Irina Negut, Anita Ioana Visan.
      Chronic wounds remain a persistent clinical challenge, trapped in a cycle of inflammation, infection, and impaired healing. While traditional dressings offer basic protection, they fail to address the complex pathophysiology of non-healing wounds. This review critically examines cellulose-based hydrogels as next-generation therapeutic platforms, analyzing their structure-property relationships, biofunctionalization strategies, and stimuli-responsive capabilities. We synthesize recent advances in antimicrobial, anti-inflammatory, and pro-regenerative hydrogels, highlighting how cellulose's inherent tunability enables precision wound management. Finally, we confront the translational barriers-including scalability, sterilization, and regulatory hurdles-that must be overcome to bridge the gap between promising biomaterial research and clinical reality. By integrating materials science with wound pathophysiology, this review provides a roadmap for developing clinically viable cellulose-based hydrogels.
    Keywords:  antimicrobial hydrogels; bacterial cellulose; cellulose hydrogels; chronic wounds; smart biomaterials; stimuli-responsive materials; tissue regeneration; wound dressings
    DOI:  https://doi.org/10.3390/gels12050410
  28. Trends Immunol. 2026 May 27. pii: S1471-4906(26)00096-7. [Epub ahead of print]
    Human antibodies as emerging drugs for antimicrobial resistance.
    Matteo Ridelfi, Vittoria Zucconi Galli Fonseca, Claudia Sala, Rino Rappuoli.
      Antimicrobial resistance (AMR) is one of today's most worrisome health emergencies. Bacteria, once easily treatable with antibiotics, have acquired resistance to many or all available drugs. In 2019, 1.27 million infection-related deaths were directly caused by AMR. By 2050, AMR could put 10 million lives per year at risk, particularly in low- and middle-income countries. This review focuses on monoclonal antibodies (mAbs) as a novel class of antimicrobials that can bypass classical resistance mechanisms and exert prophylactic and therapeutic effects. The advantages and limitations of mAbs are discussed, along with the need for rapid diagnostics for personalized use. The risk of selecting resistant strains is also addressed, as well as strategies to reduce production costs, expand global access, and improve equity.
    Keywords:  antimicrobial resistance; monoclonal antibodies; precision medicine; superbugs
    DOI:  https://doi.org/10.1016/j.it.2026.04.003
  29. Folia Microbiol (Praha). 2026 May 29.
    Isolation, genomic characterization, and biofilm eradication activity of vB_PaP_DMTU_1, a novel lytic bacteriophage against Pseudomonas aeruginosa.
    Dhirangkana Bora, Ajit Kumar Singh, Anupam Nath Jha, Manabendra Mandal.
      Biofilm-associated Pseudomonas aeruginosa (P. aeruginosa) infections pose significant therapeutic challenges owing to their intrinsic resistance to conventional antibiotics. With targeted bacterial lysis and biofilm degradation capabilities, bacteriophage therapy (phage therapy) has re-emerged as a promising alternative antimicrobial strategy. In this study, a novel lytic bacteriophage, vB_PaP_DMTU_1, was isolated from sewage wastewater in Nagaon, India, and characterized using transmission electron microscopy (TEM), whole-genome sequencing, and comprehensive biological assays. TEM micrographs revealed the podoviral morphology of the phage. Genomic analysis classified it within the Zobellviridae family and Paundecimvirus genus, containing a linear double-stranded DNA of 49 kbp with a GC content of 44.98%. Genome annotation identified 83 open reading frames (ORFs), with 25 encoding functional proteins related to structure, metabolism, infection, DNA replication, transcription regulation, packaging, and cell lysis, including 58 hypothetical proteins, one tRNA and ten Rho-dependent transcription terminator genes. The genome lacks lysogeny and CRISPR-associated genes. The phage demonstrated pH stability (6-10), UV resistance, thermal tolerance (up to 50℃), and robust lytic activity with a 30 min latent period and a burst size of ~ 100 virions per host cell. It achieved 93.58% eradication of 72 h mature biofilms at MOI = 10. Stability studies over 24 months revealed optimal phage preservation in liquid lysate formulations, followed by lyophilized powders and alginate beads. These findings establish bacteriophage vB_PaP_DMTU_1 as a promising phage therapy candidate against P. aeruginosa biofilms, significantly contributing to the arsenal of phage-based biocontrol strategies.
    Keywords:   Pseudomonas aeruginosa ; Antibiofilm; Biocontrol; Lytic bacteriophage; Phage therapy; Whole genome sequencing
    DOI:  https://doi.org/10.1007/s12223-026-01517-y
  30. Front Cell Infect Microbiol. 2026 ;16 1820133
    Pathogenicity of P. gingivalis strains carrying clusters of specific polymorphic variants of peptidylarginine deiminase gene.
    Karolina Strzelec, Agata Dziedzic-Kowalska, Klara Ferenc, Katarzyna Łazarz-Bartyzel, Iwona Olszewska-Czyż, Iwona Rąpalska, Łukasz Sieroń, Małgorzata Aptekorz, Małgorzata Romanik, Barbara Mendrek, Natalia Oleszko-Torbus, Agnieszka Kowalczuk, Damian Kusz, Tomasz Kaczmarzyk, Marta Cześnikiewicz-Guzik, Paweł Niemiec, Tomasz J Wasik, Katarzyna Gawron.
       Introduction: Periodontitis (PD) is one of the most prevalent human inflammatory diseases of bacterial etiology, affecting over 50% of adult population worldwide. It is initiated by bacterial dysbiosis and bacteria-elicited inflammation. Among key periopathogens, the anaerobic bacterium, P. gingivalis has attracted a special interest. It secretes peptidylarginine deiminase (PPAD), an enzymatic protein, which due to the conversion of arginine to citrulline residue may alter protein structure and antigenicity. Despite increasing evidence supporting involvement of PPAD in pathogenesis of PD, functional and clinical significance of ppad gene variability remains poorly understood. The goal of this work was analysis of genetic variability of ppad gene from recently collected PD cohort in the context of P. gingivalis virulence and host-pathogen interactions.
    Methods: Clinical isolates from gingival crevicular fluid (GCF) of 35 PD patients and 20 healthy donors were analyzed for the presence, sequence variability, expression, and enzymatic activity of the ppad gene in P. gingivalis using PCR, BLAST, qRT-PCR, and colorimetric assays. Virulence was assessed in murine osteoblasts (MC3T3-E1) and primary human gingival fibroblasts (PHGFs) infected with P. gingivalis clinical strains, followed by analysis of proinflammatory cytokines, PGE2-dependent pathway enzymes, and the bone resorption marker OPG.
    Results: The ppad gene of P. gingivalis strains revealed pronounced variability in PD patients, affecting gene expression and enzymatic activity. Three predominant clusters of specific polymorphic variants were identified: i) S191F + N291D, ii) S191F + N291D + S528G, iii) S203P + G231N, E232T, N235D + N291D + A515V + S528G. Infection with strains harboring the S203P + G231N, E232T, N235D + N291D + A515V + S528G resulted in elevated PPAD activity, which correlated with clinical indicators of disease severity, induced COX-2 (~6-fold) and IL-1b (~7-fold) expression in osteoblasts and led to 94% reduction in OPG. Similarly, these strains triggered upregulation of TNF-α, IL-6, COX-1, and COX-2 in PHGFs compared to the P. gingivalis ATCC 33277.
    Discussion: Collectively, these findings underscore that clusters of specific polymorphic variants of ppad are critical determinants of enzymatic function, host immune modulation and periodontal tissue destruction in PD.
    Keywords:  P. gingivalis; cluster; pathogenicity; peptidylarginine deiminase; periodontitis; polymorphic variants; virulence factors
    DOI:  https://doi.org/10.3389/fcimb.2026.1820133
  31. Biomedicines. 2026 May 14. pii: 1106. [Epub ahead of print]14(5):
    Periodontitis, Endothelial Dysfunction, and Systemic Inflammation: A Systematic Review and Meta-Analysis of Flow-Mediated Dilation.
    Cristina Ples, Cristina Savencu, Ana-Maria Pah, Gheorghe Stoichescu-Hogea, Diana-Maria Mateescu, Roxana Oancea.
      Background/Objectives: Periodontal disease is a chronic inflammatory condition associated with systemic vascular dysfunction and elevated cardiovascular risk. This systematic review and meta-analysis aimed to quantitatively evaluate the association between periodontitis and endothelial dysfunction and to assess the effects of periodontal therapy on endothelial function and inflammatory biomarkers. Methods: Conducted per PRISMA 2020 and registered in PROSPERO (CRD420261309247). Electronic databases (PubMed, Scopus, Cochrane Library) were searched for observational and interventional studies assessing endothelial function in patients with periodontitis. Risk of bias was evaluated using RoB 2, ROBINS-I, and the Newcastle-Ottawa Scale; certainty of evidence was assessed with GRADE. Pooled effects on flow-mediated dilation (FMD) and inflammatory markers were estimated using random-effects meta-analysis (DerSimonian-Laird). Results: Fourteen studies were included in qualitative synthesis; six contributed quantitative FMD data. Observational studies consistently demonstrated impaired endothelial function and elevated inflammatory markers in patients with periodontitis versus controls. Meta-analysis showed that periodontal therapy significantly improved endothelial function (pooled FMD: +3.3 percentage points; 95% CI 1.7-4.9; I2 = 77%; p < 0.001), though results should be interpreted cautiously given substantial heterogeneity and the limited number of studies (n = 6). Periodontal treatment reduced CRP levels (mean difference -0.38 mg/L; I2 = 41%); IL-6 showed a favorable direction but with very low certainty of evidence. Publication bias could not be reliably assessed given the small number of included studies. Conclusions: Periodontitis is associated with impaired endothelial function and systemic inflammation. Periodontal therapy leads to measurable improvements in both, supporting its role as a potentially modifiable contributor to cardiovascular risk. Larger randomized trials with long-term cardiovascular endpoints are warranted.
    Keywords:  C-reactive protein; cardiovascular risk; endothelial dysfunction; flow-mediated dilation; interleukin-6; meta-analysis; periodontal therapy; periodontitis; systemic inflammation; vascular function
    DOI:  https://doi.org/10.3390/biomedicines14051106
  32. Essays Biochem. 2026 May 26. pii: EBC20250035. [Epub ahead of print]
    The role of phages in plant-associated microbial communities.
    Renée E Smith, Dominique Holtappels.
      Microbial communities deliver essential functions in ecosystems. In plant environments, the plant microbiome facilitates nutrient uptake, supports plants during abiotic stress, and counteracts disease. As implementation of synthetic microbial communities becomes more of a realistic strategy for mitigating the effects of biotic and abiotic stressors on plant productivity, it is increasingly important to understand how interactions between microbes, which are essential for ecosystem function (hub microbes), are maintained. Recent research highlights the ecological role of bacteriophages, the viruses of bacteria, in host-associated microbial communities. Current evidence demonstrates the influence of the phageome on microbiomes, ranging from effects on an individual (transduction, lysogenic conversion, and evolutionary pressure) to entire populations and communities, such as Kill-the-Winner dynamics. These dynamics appear to affect the overall function of microbial communities and support plant growth. In this review, we lay out recent insights on the role of bacteriophages in plant-associated microbiomes through an eco-evolutionary lens and future directions of research to broaden our understanding of the ecological implications of bacteriophages.
    Keywords:  Bacteriophage; Microbiome; Microbiome function; Virome
    DOI:  https://doi.org/10.1042/EBC20250035
  33. J Periodontol. 2026 May 28.
    Association between oral microbial diversity and periodontitis in a nationally representative U.S. population: A cross-sectional study.
    Rui Pu, Zhikang Wang, Yunxuan Chen, Danhong Zhou, Guoli Yang, Zhiwei Jiang.
       BACKGROUND: To investigate the association between salivary oral microbiome diversity and periodontitis in a nationally representative U.S.
    POPULATION:
    METHODS: A total of 5323 participants with both periodontal examination and oral microbiome data from NHANES 2009-2012 were included. Periodontitis was defined using 2012 CDC/AAP criteria. Four alpha diversity indices (operational taxonomic unit [OTU] richness, Faith's phylogenetic diversity [FPD], the Shannon-Weiner index [SWI], and the inverse Simpson index [ISI]) were calculated. Beta diversity metrics (Bray-Curtis, weighted and unweighted UniFrac) were assessed using PERMANOVA for group comparisons and hierarchical clustering to identify subgroups. Ordered logistic regression was employed to examine the associations between periodontitis severity and microbial alpha diversity, beta diversity clusters, and bacterial genus abundances.
    RESULTS: Higher alpha diversity was positively associated with greater periodontitis severity (OTU richness: OR = 1.01, 95%CI: 1.01-1.02; FPD: OR = 1.21, 95%CI: 1.19-1.24; SWI: OR = 2.03, 95%CI: 1.81-2.30; ISI: OR = 16.61, 95%CI: 1.75-157.59). Beta diversity analyses revealed significant community compositional differences across periodontitis severity levels (PERMANOVA, all p = 0.001). Hierarchical clustering identified distinct microbial subgroups with varying odds of belonging to more severe periodontitis levels. Eighty-two bacterial genera were significantly associated with periodontitis, including taxa showing strong positive associations consistent with the red and orange complexes (e.g., Porphyromonas, Tannerella, Treponema) and taxa exhibiting negative associations involving health-associated genera (e.g., Rothia, Veillonella).
    CONCLUSIONS: Salivary microbiome diversity, particularly higher alpha diversity and specific beta diversity clusters, was associated with periodontitis severity, supporting its potential relevance as a non-invasive indicator of periodontal health status.
    PLAIN LANGUAGE SUMMARY: This national study examined the relationship between the types and quantities of microbes present in saliva and the severity of periodontitis in more than 5,300 U.S. adults. We found that the more diverse the microbial community in a person's saliva-meaning a greater variety and number of different types-the more severe their periodontitis tended to be. We also found that the composition of these microbes differed depending on the severity of the periodontitis. Specifically, certain clusters of microbes, including well-known disease-causing bacteria such as Porphyromonas and Treponema (often called the red and orange complexes), were strongly associated with more severe periodontitis. Conversely, other common, generally healthy bacteria were less abundant. These findings suggest that analyzing the diversity and composition of microbes in saliva could be a valuable, noninvasive way to check for and potentially monitor the severity of periodontitis.
    Keywords:  NHANES; alpha diversity; beta diversity; oral microbiome; periodontitis
    DOI:  https://doi.org/10.1002/jper.70101
  34. Microbiol Spectr. 2026 May 26. e0008926
    Phage Φ170 biocontrol of multidrug-resistant Vibrio parahaemolyticus in a zebrafish model.
    Wanqiu Lin, Linlin Ye, Xuhang Wang, Jianluan Ren, Feng Xue, Jianjun Dai, Fang Tang.
      Vibrio parahaemolyticus is an important zoonotic pathogen that poses a persistent threat to aquaculture systems and food safety. The rapid emergence of multidrug resistance, driven by increasing antibiotic selection pressure, highlights the urgent need for alternative antimicrobial strategies, among which phage therapy has emerged as a promising candidate. Here, we reported the isolation of a bacteriophage, designated Φ170, targeting multidrug-resistant Vibrio parahaemolyticus from sewage collected at a shrimp farm. Φ170 exhibited a latent period of 10 min, an eclipse period of approximately 60 min, and an average burst size of 426 PFU per cell. The phage also showed broad tolerance to pH and temperature. Φ170 displayed rapid and potent lytic activity, effectively suppressing host bacterial growth within 6 h post-infection. To further assess its in vivo efficacy, we evaluated the prophylactic and therapeutic potential of phage administration by immersion in zebrafish challenged with Vibrio parahaemolyticus. Prophylactic treatment with Φ170 significantly increased zebrafish survival within 72 h. Moreover, combined treatment with Φ170 and doxycycline exerted a synergistic effect, effectively reducing bacterial loads, alleviating liver and intestine tissue damage, and suppressing excessive inflammatory responses. Collectively, these findings indicated that phage Φ170 represented a promising prophylactic agent against Vibrio parahaemolyticus infection and that combined phage therapy with antibiotics provided an effective strategy for treating drug-resistant Vibrio parahaemolyticus infections.IMPORTANCEPhage therapy is a promising strategy for combating bacterial infections, serving as a complementary therapy to antibiotics and a synergistic approach in combination treatments with antimicrobial agents. To address infections by multidrug-resistant (MDR) Vibrio parahaemolyticus, we isolated and characterized bacteriophage Φ170, which is capable of lysing MDR Vibrio parahaemolyticus. We evaluated its prophylactic and therapeutic potential in a zebrafish infection model. We found that phage Φ170 exhibited strong lytic activity both in vitro and in vivo, effectively preventing Vibrio parahaemolyticus infection and displaying synergistic antibacterial effects when combined with antibiotics. Phage-antibiotic combination therapy further enhanced therapeutic efficacy in infected zebrafish. Our results provide experimental support for phage-antibiotic combination strategies against MDR bacterial infections and highlight the potential of phage therapy for the prevention and treatment of Vibrio parahaemolyticus infections.
    Keywords:  Vibrio parahaemolyticus phage; multidrug-resistant Vibrio parahaemolyticus; phage prevention and treatment; zebrafish model
    DOI:  https://doi.org/10.1128/spectrum.00089-26
  35. Adv Healthc Mater. 2026 May 28. e71297
    Self-Powered Piezoelectric Nanofibrous Hydrogel for Synergistic Electro-Pharmacological Therapy of Chronic Wounds.
    Baoyu Wang, Yuting Wang, Meiying Li, Chubin Wan, Xin Ju, Can Cao, Ruodan Xu, Ning Li.
      Chronic wounds such as diabetic foot ulcers and burns pose clinical challenges due to persistent inflammation and impaired endogenous bioelectric signaling. Here, we report a self-powered piezoelectric nanofibrous hydrogel for synergistic electro-pharmacological therapy, fabricated via dual-nozzle electrospinning and Ca2+ crosslinking. This therapeutic paradigm facilitates a dual-action mechanism that integrates direct biophysical stimulation with electro-kinetically accelerated drug delivery, both driven autonomously by physiological motion. This platform integrates a β-phase-rich poly(vinylidene fluoride-co-trifluoroethylene) (PVDF-TrFE) matrix with an ion-crosslinked polyvinyl alcohol-sodium alginate (PVA-SA) hydrogel, successfully transforming a hydrophobic interface into a hydrophilic one and matching human skin's modulus (1.8-2.1 MPa). By encapsulating immunomodulator resveratrol (RSV) and bactericidal silver nanoparticles (Ag NPs), the dressing converts biomechanical energy into therapeutic bioelectric potentials (0.3-3.0 V). Mechanistically, the motion-induced piezoelectric field generates electro-kinetic driving forces that actively upregulate the transport rate constant (K) by reducing the energy barrier for molecular diffusion, thereby accelerating RSV bioavailability beyond passive diffusion. In a Staphylococcus aureus-infected chronic wound model, the synergy significantly facilitates wound closure (95.8% vs 63.3% by day 10) by effectively suppressing inflammation, promoting angiogenesis, and accelerating collagen maturation, with excellent biocompatibility and no systemic toxicity. This study establishes a scalable strategy for recalcitrant inflammatory injuries and motion-associated pathologies.
    Keywords:  bioelectric signals; chronic wound healing; motion‐driven therapy; piezoelectric hydrogel; synergistic therapy
    DOI:  https://doi.org/10.1002/adhm.71297
  36. Front Microbiol. 2026 ;17 1747931
    CRISPR-Cas systems as next-generation antimicrobials: a systemic review of mechanisms, delivery strategies, and translational challenges.
    Maha S I Wizrah.
       Introduction: The rapid global increase in multidrug-resistant (MDR) bacteria has compromised the effectiveness of conventional antibiotics, stressing the urgent need for alternative antimicrobial strategies. CRISPR-Cas systems, originally evolved as bacterial adaptive immune mechanisms, provide programmable and highly specific tools for targeting antimicrobial resistance (AMR) determinants.
    Objective: This systematic review aims to evaluate the antibacterial mechanisms, delivery strategies, preclinical evidence, safety considerations, and translational potential of CRISPR-Cas systems for combating MDR bacterial infections.
    Methods: A systematic literature search was conducted in PubMed, Scopus, Cochrane Library, and Web of Science up to January 2026 in accordance with PRISMA 2020 guidelines. Eligible studies included original in vitro and in vivo experimental or preclinical investigations assessing CRISPR-Cas systems (Cas9, Cas12, Cas13, or related effectors) for antibacterial activity or antibiotic resensitization. Data were extracted on CRISPR effector type, bacterial target, delivery platform, and therapeutic outcome. Due to methodological heterogeneity, results were synthesized narratively.
    Results: Most studies reported effective killing or resensitization of MDR bacteria through chromosomal double-strand break induction, resistance plasmid curing, integron disruption, or RNA-targeted cleavage. Cas9 was the most frequently employed effector, followed by Cas12 and Cas13. Delivery strategies included bacteriophages, conjugative plasmids, and nanoparticle-based systems, with phage-mediated delivery demonstrating the most consistent efficacy in complex environments and animal models. Notably, a CRISPR-enhanced engineered bacteriophage cocktail (LBP-EC01) has advanced to clinical evaluation.
    Discussion: Overall, the evidence supports CRISPR-Cas antimicrobials as a promising precision-based approach for addressing AMR. However, major barriers remain, including limited host range, instability in physiological environments, emergence of escape mutations, and insufficient data on off-target effects and long-term safety. Addressing these challenges through optimized delivery platforms, multiplex targeting strategies, and standardized safety and regulatory frameworks will be essential for clinical translation.
    Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261319789, identifier CRD4201319789.
    Keywords:  CRISPR–Cas; anti-CRISPR; antimicrobial resistance; multidrug resistance; phage delivery; plasmid curing; synthetic biology
    DOI:  https://doi.org/10.3389/fmicb.2026.1747931
  37. BMJ Open. 2026 May 24. 16(5): e118771
    Reducing the impact of diabetic foot ulcers (REDUCE): study protocol for an effectiveness and cost-effectiveness randomised controlled trial with embedded process evaluation.
    Natasha Mitchell, Kavita Vedhara, Kieran Ayling, Alex Mitchell, Christina Sheehan, Katherine Cullen, Ruth Hart, Azeezat Adenike Okanlawon, Catherine Arundel, Katherine Bradbury, Debbie Brewin, Trudie Chalder, Nicky Cullum, Colin Dayan, Grazziela Figueredo, Deborah Fitzsimmons, Catherine Hewitt, Glen Howard, Julia Lawton, Chris Metcalfe, David Torgerson, Judith Watson, Kirsty Winkley, Lucy Yardley, Frances Game.
       INTRODUCTION: Diabetic foot ulceration represents a prevalent, persistent and resource-intensive complication of diabetes. These ulcers are slow to heal, prone to recurrence and impose a substantial burden on both patients and healthcare providers. The reducing the impact of diabetic foot ulcers (REDUCE) intervention has been designed as a multifaceted approach targeting psychological and behavioural determinants linked to diabetic foot ulcer (DFU) outcomes. Following a successful pilot trial, the REDUCE trial has been designed as a pragmatic, multicentre randomised trial to compare the effectiveness and cost-effectiveness of the REDUCE intervention plus usual care versus usual care alone in reducing recurrence in people with healed DFUs. Additionally, there is an embedded process evaluation and two sub-studies which will be carried out alongside the main trial.
    METHODS AND ANALYSIS: Adults over 18 years of age, with a recently healed DFU and two lower limbs, will be identified from around 30 specialist multidisciplinary diabetic foot clinics at participating National Health Service Trusts in the UK. Patients with active Charcot neuro-osteoarthropathy, active DFU or ulcers healed for more than 12 weeks will be excluded. We will aim to recruit 544 participants (1:1 randomisation). The primary outcome for this trial will be total ulcer-free days with limbs intact (ie, without amputation) between randomisation and the end of follow-up (18 months post-randomisation). Secondary outcomes include time to re-ulceration, total number of ulcers, amputation, quality of life (EQ-5D-5L), Patient Health Questionnaire-9, Nottingham Assessment of Functional Footcare, ICEpop capability measure for adults and resource use. As part of the process evaluation, up to 20 REDUCE intervention patient-participants will be interviewed, and the healthcare professionals delivering the intervention will also be interviewed. An assessment of intervention fidelity will also be carried out.
    ETHICS AND DISSEMINATION: Ethics approval was granted by Wales 3 Research Ethics Committee (REC reference 22/WA/0053) on 16 March 2022. The findings will be presented at relevant conferences and disseminated via peer-reviewed research publications and to relevant stakeholders.
    TRIAL REGISTRATION NUMBER: ISRCTN15570706.
    Keywords:  Community-Based Participatory Research; Diabetic foot; Randomized Controlled Trial
    DOI:  https://doi.org/10.1136/bmjopen-2026-118771
  38. Nat Rev Dis Primers. 2026 May 28. pii: 33. [Epub ahead of print]12(1):
    Osteomyelitis.
    Sandra R Arnold, Vincenzo Giordano, William T Obremskey, Edward M Schwarz, Mark S Smeltzer, Deborah J Veis, James E Cassat.
      Osteomyelitis, defined as inflammation of bone, is a highly morbid disease that is most commonly caused by bacterial infection. Infectious osteomyelitis occurs across a spectrum of ages and affects previously healthy individuals as well as individuals with medical comorbidities. Establishment of osteomyelitis typically occurs following one of three general pathological mechanisms, including haematogenous seeding of healthy or injured bone, extension of a contiguous soft tissue infection, or direct inoculation of microorganisms into the bone following trauma. A wide spectrum of microbial pathogens can cause osteomyelitis in these settings. The most common aetiologies share common pathogenic traits such as the propensity to form biofilms, the elaboration of immunoevasive toxins and virulence factors, and the ability to adhere to and invade bone tissue. Challenges in diagnosing, prognosing and treating osteomyelitis remain owing to limitations of conventional cultures, absence of faithful biomarkers, inability to delineate acute versus chronic infection, and therapeutic recalcitrance. Despite prolonged antimicrobial therapy, many individuals with osteomyelitis fail treatment and go on to develop highly morbid complications. Improvements in the management of osteomyelitis will require an ongoing commitment to multidisciplinary clinical care, basic and translational research to uncover pathophysiological mechanisms of disease, and sustained investments in new approaches for the diagnosis, treatment and mitigation of complications.
    DOI:  https://doi.org/10.1038/s41572-026-00707-9
  39. J Clin Med. 2026 May 13. pii: 3754. [Epub ahead of print]15(10):
    Association Between Diabetic Foot Lesions and Diabetic Foot Ulcers: A Cross-Sectional Study.
    Moe Murai, Yoshitaka Hashimoto, Haruka Utsuyama, Takashi Ogasawara, Akifumi Shiota, Nozomi Yoshioka, Yusuke Hamazawa, Michiaki Fukui.
      Aims: The purpose of this study was to clarify the prevalence of diabetic foot lesions and their association with lower-limb amputations and/or foot ulcers. Materials and Methods: In this cross-sectional study, 968 patients with diabetes were surveyed. Diabetic foot lesions were defined according to the broad national criteria, which encompass both mild abnormalities and more advanced conditions. Based on this definition, foot lesions were assessed using a questionnaire comprising the following 10 items: a history of lower-limb amputations, a history of treatment of foot lesions, numbness/loss of sensation/pain, skin discolorations, skin symptoms, nail abnormalities, foot ulcers/gangrene, foot deformities, foot infection, and intermittent claudication. Logistic regression analysis was used to examine risk factors for foot lesions. Area under the curve (AUC) of the number of foot lesions for lower-limb amputations or foot ulcers/gangrene was calculated using the receiver operating characteristic curve (ROC) analysis. Results: Approximately two-thirds of the patients had at least one type of diabetic foot lesion. Logistic regression analysis revealed that women, past or current smoking, a history of cardiovascular disease, and nephropathy were associated with the risk of diabetic foot lesions. According to the ROC analysis, the optimal cut-off point of number of diabetic foot lesions was three for identifying patients with a history of lower-limb amputation and/or the presence of foot ulcers or gangrene (AUC 0.80 (95% CI, 0.70-0.91), p < 0.01). Conclusions: Diabetic foot lesions are common in patients with diabetes and the prevalence of diabetic foot lesions was higher in patients with a history of lower-limb amputations and/or the presence of foot ulcers or gangrene. Early detection and care of diabetic foot lesions are necessary to prevent lower-limb amputations and foot ulcers.
    Keywords:  diabetic foot lesions; diabetic foot ulcers
    DOI:  https://doi.org/10.3390/jcm15103754
  40. Front Pharmacol. 2026 ;17 1773609
    Artificial intelligence for coordinating vaccine design, antiviral discovery, and real-world monitoring in the era of emerging and endemic viral threats.
    Adewunmi Akingbola, Abiodun Adegbesan, Olajumoke Adewole, Kehinde O Adebiyi, Akpevwe Emmanuel Benson, Olajide Ojo, Jessica Otumara Urowoli, Opeyemi Joshua Alabi, Oluwaremilekun Juliet Ojeriakhi, Mayowa Shekoni.
      Vaccine development has traditionally been a lengthy and resource-intensive process, often struggling to keep pace with rapidly emerging infectious threats. Recent advances in artificial intelligence (AI) offer new opportunities to transform this landscape by enabling faster, more precise, and data-driven approaches to vaccine design. This review examines how AI is being applied across key stages of vaccine development, including antigen discovery, epitope prediction, structural optimisation, immunogenicity assessment, and safety evaluation. We highlight the use of machine learning and deep learning models to analyse large-scale genomic, proteomic, and immunological datasets, allowing for more targeted identification of promising vaccine candidates. While AI-driven approaches show considerable promise, their successful translation into effective vaccines depends on the quality and representativeness of the data used, as well as close integration with experimental and clinical validation. Current challenges include data bias, limited representation of populations from low- and middle-income countries, and the need for transparent and interpretable models that can support regulatory decision-making. By synthesising recent developments and ongoing challenges, this review underscores the potential of AI to complement traditional vaccine development pipelines. When responsibly implemented, AI-based methods may accelerate vaccine innovation, improve global preparedness, and support more equitable responses to future infectious disease outbreaks.
    Keywords:  artificial intelligence; global health preparedness; infectious diseases; machine learning; pandemics; vaccine design
    DOI:  https://doi.org/10.3389/fphar.2026.1773609
  41. J Med Internet Res. 2026 May 29. 28 e101366
    From Virtual Molecules to Clinical Trials: How AI Is Reshaping Preclinical Drug Discovery.
    Benedette Cuffari.
       Unlabelled: Pharmaceutical development is typically a long and arduous process, but advances in artificial intelligence may help streamline each stage of this pipeline. In this News and Perspectives article, JMIR Correspondent Benedette Cuffari reports on recent innovations and their potential implications for drug discovery.
    Keywords:  artificial intelligence in drug discovery; computational drug discovery; de novo drug design; generative chemistry; machine learning in drug design
    DOI:  https://doi.org/10.2196/101366
  42. Int J Nanomedicine. 2026 ;21 603447
    Natural Compound-Loaded PLGA Nanocarriers for Infected Wound Management: A Review.
    Elahe Norouzi, Jaber Hemmati, Mohammad Chehelgerdi, Mohammad Reza Arabestani.
      Infected wounds remain a significant clinical challenge due to persistent microbial colonization, biofilm formation, delayed tissue regeneration, and prolonged healing processes. Poly (lactic-co-glycolic acid) (PLGA), a biodegradable and biocompatible polymer approved by the FDA, has gained increasing attention as a carrier for natural compounds because of its ability to provide controlled and sustained drug release, improve compound stability, and enhance therapeutic efficacy. This review summarizes recent advances in PLGA-based formulations loaded with natural compounds for the treatment of infected wounds. Findings from various studies demonstrate that these nanostructures promote wound healing through antimicrobial and anti-biofilm activities, antioxidant and anti-inflammatory effects, stimulation of angiogenesis, collagen deposition, and re-epithelialization. In addition, this review discusses different aspects of PLGA-based nanostructures, including fabrication and synthesis strategies, drug release behaviors, and bacterial biofilm-targeting mechanisms, which may play an important role in the development of novel nanoparticle-based therapeutic approaches for overcoming current challenges associated with infected wound management. Overall, the delivery of natural compounds through PLGA-based systems represents a promising strategy for the effective treatment of infected wounds and the advancement of next-generation wound care therapies. This review, with a focus on PLGA-natural compound systems for the treatment of infected wounds, provides a coherent synthesis of dispersed studies and, by emphasizing antibiofilm mechanisms and controlled drug release, offers an integrated perspective for a better understanding of the therapeutic potential of these nanoplatforms.
    Keywords:  PLGA; anti-inflammatory; antioxidant; natural compounds; wound
    DOI:  https://doi.org/10.2147/IJN.S603447
  43. Front Pharmacol. 2026 ;17 1775585
    Sepsis in end-stage liver disease and acute-on-chronic liver failure: pathophysiology, diagnostic challenges, and pharmacological management.
    Jacopo Belfiore, Riccardo Taddei, Lorenzo Roberto Suardi.
       Background: Sepsis represents a leading cause of acute decompensation, acute-on-chronic liver failure (ACLF), and short-term mortality in patients with end-stage liver disease (ESLD). Its clinical course is shaped by the coexistence of profound systemic inflammation, cirrhosis-associated immune dysfunction (CAID), and early multiorgan failure, which together complicate diagnosis, antimicrobial management, and supportive care.
    Methods: This narrative review synthesizes current evidence on the epidemiology, immunopathophysiology, microbiology, diagnostic strategies, and therapeutic management of sepsis in patients with ESLD and ACLF, with a specific focus on pharmacological considerations, antimicrobial resistance, biomarker-guided diagnosis, and emerging immunomodulatory and extracorporeal therapies.
    Results: Patients with ESLD and ACLF exhibit a dynamic immune phenotype characterized by impaired innate and adaptive immune responses alongside persistent systemic inflammation, predisposing them to severe infections and sepsis. Multidrug-resistant bacterial pathogens and invasive fungal infections are increasingly prevalent and significantly worsen outcomes. Although rapid molecular diagnostics and selected biomarkers improve early pathogen identification and risk stratification, their diagnostic accuracy remains limited by baseline inflammation and hepatic dysfunction. Empirical antimicrobial therapy must balance early broad-spectrum coverage with antimicrobial stewardship, accounting for altered pharmacokinetics and pharmacodynamics. Supportive strategies-including optimized fluid resuscitation, vasopressor therapy, renal replacement techniques, and extracorporeal blood purification-remain central, whereas immune-modulating therapies such as granulocyte colony-stimulating factor, interleukin-1 blockade, and intravenous immunoglobulins are biologically plausible but not yet supported by robust clinical evidence.
    Conclusion: Sepsis in ESLD and ACLF is a complex, high-risk condition requiring an integrated, multidisciplinary approach that combines early diagnosis, individualized pharmacological strategies, and tailored organ support. Despite advances in diagnostics and supportive care, outcomes remain poor, underscoring the urgent need for disease-specific clinical trials to refine antimicrobial strategies and evaluate targeted immunomodulatory interventions in this vulnerable population.
    Keywords:  acute-on-chronic liver failure; antimicrobial pharmacotherapy; cirrhosis-associated immune dysfunction; immunomoulation therapy; sepsis
    DOI:  https://doi.org/10.3389/fphar.2026.1775585
  44. Br J Hosp Med (Lond). 2026 May 20. 87(5): 54065
    The Diagnostic Complexities of Cystic Fibrosis: When to Think of It and What to Do?
    Ladina Weitnauer, Nicholas J Simmonds.
      Cystic fibrosis (CF) is one of the most common life-shortening hereditary disorders, caused by a defect in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This defect causes multi-system disease, but primarily it affects the lungs and pancreas. Over 2000 CFTR gene variants have been identified; these can result in variable CFTR protein function and, consequently, a diverse clinical phenotype. CF is not only diagnosed in children but also in adults and is present in non-White populations. In adults, CF often presents with an atypical phenotype, usually due to residual CFTR protein function, which can be caused by rare CFTR variants. As a result, diagnosing CF in adults can be challenging. In this review, we discuss who should be considered for CF, how and where the diagnosis is made, and why a timely CF diagnosis is important for all patients, as well as their families.
    Keywords:  CFTR-related disorder; cystic fibrosis; diagnosis; intestinal current measurement; nasal potential difference; sweat chloride concentration
    DOI:  https://doi.org/10.31083/BJHM54065
  45. Antonie Van Leeuwenhoek. 2026 May 28. pii: 136. [Epub ahead of print]119(7):
    Intervening at the microbial crossroads: targeting inflammation across the oral-gut-reproductive microbiome crosstalk in atherosclerosis.
    Wahid Adeoye Saka, Precious Adeoye Oyedokun, Timileyin Abdul-Mumeen Alade, Bobola Timothy Oyeleke, Abraham Ololade Oyelaran, Marvelous Dasola Oyedokun, Chidinma Angela Irozuoke, Oluwaseyi Mary Olayemi, Seun Oladepo, James Ajigasokoa Ndako.
      Despite the increasing burden of mortality due to cardiovascular disease, the traditional risk factors fail to explain the complexity of the pathology of cardiovascular disease, especially in the context of chronic inflammation. Emerging scientific evidence indicates that dysbiosis of the oral, gut, and reproductive microbiome is associated with systemic vascular dysfunction. This review comprehensively discusses the available scientific data on the interactions between the mucosal colonizing microbiota and their modulation of whole-body inflammation and cardiovascular disease pathogenesis. It underlines the roles of microbial metabolites, including trimethylamine N-oxide and lipopolysaccharides, in immune activation, epithelial barrier cell injury, and their effects in endothelial activation, vascular remodeling and dysfunction, oxidative stress, and inflammation. This review describes the mechanistic interplay that drives atherosclerosis and vascular dysfunction, mediated by immune activation and cytokine-driven inflammatory cascades. Sex hormones influence the composition of the microbiota and the host immune responses, thereby influencing vascular disease manifestations and responses to therapy. These mechanisms present the potential of intervening at the microbial crossroads through microbiome-targeted approaches as an effective treatment strategy for cardiovascular disease.
    Keywords:  Cardiovascular disease (CVD); Endothelial dysfunction; Microbial dysbiosis; Microbiota-targeted therapy; Oral-gut-reproductive axis; Vascular remodeling
    DOI:  https://doi.org/10.1007/s10482-026-02349-z
  46. Ann Intensive Care. 2026 ;16 100085
    Alveolar dysregulation of host response in pneumonia and ARDS: implications for immune modulation and infection.
    L S Boers, L Maessen, J Wauters, E D Morrell, A Sarma, A Conway Morris, L D J Bos.
       Background: Respiratory failure due to pneumonia and acute respiratory distress syndrome (ARDS) remains a major cause of morbidity and mortality in the intensive care unit. The alveolar compartment plays a central role in both pathogen clearance and tissue injury, yet its biology is poorly captured by systemic measurements. Growing evidence shows that dysregulation of alveolar host responses drives disease progression, shapes susceptibility to secondary infections, and influences recovery.
    Main body: Community-, hospital-, and ventilator-associated pneumonia differ in microbial drivers and host responses, but all share a pattern of localized inflammation. In most cases, pathogens are rapidly controlled following antimicrobial treatment, while alveolar inflammation persists. This persistence likely reflects self-reinforcing cycles between epithelial injury, neutrophil activity, and monocyte-macrophage dysfunction. Mechanical ventilation further disrupts local defenses, promoting microbial overgrowth and ventilator-associated pneumonia.In ARDS, diffuse alveolar damage initiates an early influx of neutrophils and monocyte-derived macrophages. Although peripheral blood has been used to identify systemic inflammatory subphenotypes, molecular signatures in the alveolar compartment often differ and may provide complementary biological information. Patients may diverge into distinct alveolar immune trajectories, ranging from sustained alveolar hyperinflammation to immune exhaustion. These divergent trajectories influence downstream repair, determining whether patients achieve epithelial recovery or develop fibrotic remodeling.Alveolar immune dysregulation also creates a permissive niche for viral and fungal pathogens. Pulmonary reactivation of herpes simplex virus or cytomegalovirus and fungal infections with Aspergillus frequently occur in critically ill patients and may reflect impaired local host defense. These processes are associated with prolonged mechanical ventilation and illustrate how impaired alveolar defenses may sustain injury and propagate complications.
    Conclusion: Pneumonia and ARDS share common pathways of alveolar immune dysregulation that are not adequately captured by systemic profiling alone. Integrating systemic and alveolar immune assessment, including their concordance and discordance, may improve patient stratification, facilitate identification of treatable traits, and support the development of more personalized, compartment-informed therapeutic strategies, including both immunomodulatory and pathogen-directed interventions. A more refined understanding of compartment-specific host responses will be key to advancing these approaches.
    Keywords:  ARDS; Alveolar host response; Alveolar injury; Immune dysregulation; Pneumonia
    DOI:  https://doi.org/10.1016/j.aicoj.2026.100085
  47. Dermatol Ther (Heidelb). 2026 May 29.
    The Gut-Oral-Skin-Heart Microbiota Axis and Oxidative Stress: Where Have We Been and Where Are We Going.
    Irena Girna, Alicja Kuban-Jankowska, Anna Jakubczyk-Slabicka, Adam Kosiński, Marcin Gruchała, Magdalena Górska-Ponikowska.
      Scientific interest in the relationship between cardiovascular disease and the human microbiome has grown substantially in recent years, with particular emphasis placed on the gut microbiota. Emerging evidence suggests, however, that distinct microbial niches-including the skin, oral cavity, and gut-may interact to influence cardiovascular homeostasis through shared pathogenic pathways, most notably oxidative stress and systemic inflammation. Intestinal dysbiosis has been strongly linked to the increased production of microbial metabolites such as trimethylamine N-oxide, which promotes endothelial dysfunction, oxidative imbalance, and atherogenesis. The oral microbiome has similarly been implicated in cardiovascular pathology through mechanisms encompassing chronic low-grade inflammation, transient bacteremia, and direct vascular colonization by pathogenic species. The contribution of the skin microbiome to cardiovascular risk remains less well defined; nevertheless, chronic inflammatory dermatoses-psoriasis in particular-have been consistently associated with elevated cardiovascular risk, a relationship potentially mediated by systemic immune dysregulation and oxidative stress. This review synthesizes current evidence on the gut-oral-skin-cardiac microbiome axis, underscoring the central role of oxidative stress as a convergent pathogenic mechanism and examining potential therapeutic implications. A more comprehensive understanding of these interconnected systems may inform the development of novel, microbiome-targeted strategies for the prevention and management of cardiovascular disease.
    Keywords:  Cardiovascular diseases; Gut microbiome; Oral microbiome; Oxidative stress; Skin microbiome; Trimethylamine N-oxide (TMAO)
    DOI:  https://doi.org/10.1007/s13555-026-01794-y
  48. Pathogens. 2026 Apr 26. pii: 469. [Epub ahead of print]15(5):
    Neonatal Infections Caused by Multidrug-Resistant Bacteria: An Analysis of Prevalence, Risk Factors, and Therapeutic Implications-A Narrative Review.
    Elena-Teona Coșovanu, Teodora Ana Balan, Eric-Oliviu Coșovanu, Silvia Ionescu, Costin Damian, Antoneta Dacia Petroaie, Elena-Adorata Coman, Mihaela Grigore, Demetra Socolov, Raluca Anca Balan, Luminita Smaranda Iancu, Irina Draga Căruntu, Ramona Gabriela Ursu.
      Neonatal infections remain a leading cause of morbidity and mortality worldwide, particularly among preterm and low-birth-weight infants and in low- and middle-income countries. This burden has intensified with the global increase in multidrug-resistant (MDR) bacteria, especially in neonatal intensive care units, where prolonged hospitalization, invasive interventions, and exposure to broad-spectrum antibiotics promote colonization, transmission, and invasive infection. In this narrative review, we explore the epidemiology and microbiological characteristics of MDR bacterial infections in newborns, alongside their associated risk factors, diagnostic challenges, treatment outcomes, and prevention strategies. Across different settings, Gram-negative pathogens, particularly Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii, account for a substantial proportion of severe neonatal infections, whereas methicillin-resistant Staphylococcus aureus remains important in selected units. The risk of MDR infection is driven by a complex interplay of factors, ranging from maternal and perinatal exposures to the inherent immunological vulnerability of newborns, hospital-based transmission, antibiotic selection pressure, and structural deficiencies in healthcare infrastructure. Diagnosis remains challenging because clinical presentations are nonspecific and culture-based methods are constrained by low blood volumes, prior antimicrobial exposure, and delayed turnaround times. Treatment is increasingly complicated due to resistance to standard empirical regimens, substantial regional variation in susceptibility profiles, and limited neonatal pharmacokinetic and safety data for reserve agents. Current evidence mainly supports surveillance-informed empirical therapy, susceptibility-guided treatment adjustment, antimicrobial stewardship, and strict infection prevention measures. Future progress will require neonatal-specific clinical trials, harmonized surveillance systems, stronger molecular epidemiology, and more equitable access to microbiological diagnostics and effective treatment.
    Keywords:  Gram-negative bacteria; NICU; antimicrobial resistance; antimicrobial stewardship; infection prevention; multidrug resistance; neonatal sepsis; neonatal therapeutics
    DOI:  https://doi.org/10.3390/pathogens15050469
  49. Expert Rev Anti Infect Ther. 2026 May 28. 1-14
    Disruptive innovation in antibiotic development: a vision for lysins.
    Yves Briers.
       INTRODUCTION: Antimicrobial resistance is escalating globally, while the development of new antibiotic classes has stagnated. This trend is reminiscent of the late-stage dynamics of S-curve innovation, where incremental advances no longer meet clinical needs. To overcome this impasse, disruptive innovation is required. As protein-based antibacterials, lysins represent a fundamentally different modality from traditional small-molecule antibiotics and offer new opportunities for disruptive innovation in terms of resistance development and microbiome preservation.
    AREAS COVERED: Sourced from a vast natural reservoir, lysins exhibit rapid, targeted bactericidal activity with low resistance potential and high specificity. Their narrow-spectrum nature supports a potential for microbiome preservation and the conceptual development of theranostic platforms for precision infectious disease management, combining ultra-fast pathogen detection with targeted therapeutic activity.
    EXPERT OPINION: To initiate new innovation cycles, disruptive modalities such as protein-based lysins will be needed, offering a paradigm shift in antimicrobial therapy. Their modular architecture and amenability to protein engineering enable a hit-to-lead development strategy akin to small-molecule pipelines. Their synergistic interactions with standard-of-care antibiotics and booster-like activity could facilitate incremental clinical integration into existing treatment protocols. This positioning supports regulatory acceptance and paves the way for lysins to become transformational components of precision antimicrobial therapy.
    Keywords:  Lysin; antibiotic development; disruptive innovation; endolysin; microbiome preservation; synergy; theranostics
    DOI:  https://doi.org/10.1080/14787210.2026.2680018
  50. bioRxiv. 2026 May 17. pii: 2026.05.14.725151. [Epub ahead of print]
    Counting to two: how phages decide between lysis and lysogeny.
    Janni Harju, Ghita Guessous, Zemer Gitai, Ned Wingreen.
      Upon infecting a bacterium, temperate phages must decide between killing the cell to reproduce (lysis) or entering a symbiotic lifestyle (lysogeny). This choice is often informed by the cell's state, as well as the number of infecting phage particles (MOI). Since phage gene copy numbers scale identically with MOI, an MOI-dependent decision requires a fast-acting asymmetry between the lytic and lysogenic pathways. We introduce a minimal model suggesting that only a handful of coupling mechanisms can produce such an asymmetry; for instance via a host protease, kinase, or RNase acting on one pathway. By distilling complex regulatory networks to their essential components, our model clarifies the logic of lysis-lysogeny decision mechanisms across phage species.
    DOI:  https://doi.org/10.64898/2026.05.14.725151
  51. Diseases. 2026 Apr 29. pii: 158. [Epub ahead of print]14(5):
    Physiotherapy Intervention for Diabetic Foot Ulcers: A Scoping Review.
    Shinsuke Imaoka, Shohei Minata, Taisuke Teroh, Kotaro Matsuki, Ryotaro Hiramatsu.
       BACKGROUND/OBJECTIVES: Understanding the available interventions and circumstances under which physical therapy is administered to patients with diabetic foot ulcers is important to provide more evidence regarding physical therapy and associated outcomes in this population. This study aimed to investigate the scope, nature, and extent of literature on physical therapy interventions for adults with diabetic foot ulcers.
    METHODS: Articles on physiotherapy interventions for adults with diabetic foot ulcers published up to 30 June 2024 were included. Relevant articles were identified through searches of PubMed, Scopus, MEDLINE, and the Cochrane Library databases. Opinion articles, study protocols, meeting abstracts, and articles that did not describe physical therapy interventions were excluded.
    RESULTS: The systematic search identified 13 articles that met the inclusion criteria. Eleven of the 13 articles were specifically related to outpatient physical therapy. Outpatient physiotherapy included unloading gait instruction, ankle stretching instruction, progressive resistance training, and aerobic exercise. In two other cases, exercise instructions were practiced in the early postoperative period of the wound during the hospitalization period. A multidisciplinary approach aimed at improving postoperative activities of daily living was included. The main efficacy indices were the wound reduction rate, plantar pressure reduction, hemodynamics, ankle joint range of motion, walking ability, and other physical function-related parameters.
    CONCLUSIONS: Physiotherapy during outpatient follow-up may contribute to preventing wound deterioration and maintaining physical function in patients with stable DFUs. However, standardized protocols regarding intervention timing, exercise intensity, and wound severity remain unestablished, and interventions should be applied cautiously based on individual clinical conditions.
    Keywords:  diabetic foot ulcers; intervention; physiotherapy; scoping review
    DOI:  https://doi.org/10.3390/diseases14050158
  52. Infect Prev Pract. 2026 Jun;8(2): 100531
    Optimizing antimicrobial stewardship in urology: a qualitative study on needs, values and requirements for clinical decision support.
    E M Engel-Dettmers, L M A Braakman-Jansen, J E W C van Gemert-Pijnen, R M Verdaasdonk.
       Background: Urinary tract infections (UTIs) are an important driver of antimicrobial use. Despite antimicrobial stewardship (AMS) initiatives, adherence to treatment guidelines remains poor. Clinical decision support systems (CDSSs) may enhance this, but require alignment with user needs for uptake.
    Aim: To explore the experiences, challenges and support needs of urologists in UTI management to identify design requirements for AMS-related CDSSs.
    Methods: A qualitative focus group study was conducted among physicians at a Dutch teaching hospital. During two sessions, diagnostic and treatment challenges were explored to elicit motivations for AMS and requirements for decision support. A multi-disciplinary research team used thematic analysis and requirements mapping methods for analysis.
    Findings: Participants face multi-faceted challenges in infection treatment, mainly due to missing data and insufficient knowledge, leading to uncertainty in treatment choices. They expressed a need for support, motivated by the desire to improve patient care and increase workflow efficiency, and by the notion to consider antimicrobial resistance (AMR) in prescribing practices. Values for the design of CDSSs are quality of care, efficiency and professional autonomy, translated into requirements for functional properties, user experience and integration into the organizational structure.
    Conclusion: Optimizing infection treatment requires an approach that balances effective individual antimicrobial therapy with public health priorities, such as AMR reduction. CDSSs can provide valuable support in this regard, provided that development and implementation are designed with clinical relevance, ease of use, and legal accountability in mind. Addressing the challenges and integrating the requirements from this study into CDSS development helps to create a sustainable and effective AMS strategy.
    Keywords:  Antimicrobial stewardship; Clinical decision support; Needs and requirements; Urology
    DOI:  https://doi.org/10.1016/j.infpip.2026.100531
  53. Pathogens. 2026 Apr 22. pii: 452. [Epub ahead of print]15(5):
    Differential Evolution of Achromobacter spp. Isolates in Upper and Lower Airways of People with Cystic Fibrosis.
    Laura Veschetti, Angela Sandri, Giulia Maria Saitta, Marzia Boaretti, Paola Melotti, Cristina Cigana, Alessandra Bragonzi, Maria M Lleò, Giovanni Malerba, Caterina Signoretto.
      Achromobacter spp. are opportunistic pathogens in people with cystic fibrosis (PwCF), yet the role of the upper airways in their persistence and adaptation remains poorly understood. We investigated whether the sinonasal compartment may act as reservoir and evolutionary niche for Achromobacter spp. during airway infection. Twenty-two isolates obtained from paired nasal lavage and sputum samples of seven PwCF were analysed by whole-genome sequencing. Within each PwCF, identical clone types were detected in both airway compartments, supporting bacterial exchange between upper and lower airways. Despite clonal relatedness, substantial genomic diversification was observed between paired isolates. Genomic signatures indicative of elevated mutation rates were detected in a high number of isolates (73%) and in both airway compartments, highlighting widespread genomic diversification across the respiratory tract. Mobilome analysis revealed compartment-specific variations in insertion sequences, prophages, and integrative elements, suggesting genome plasticity. Additionally, mutation in an aspartate kinase gene was consistently associated with loss of biofilm formation in vitro, highlighting a potential link between this pathway and biofilm phenotype. Overall, our findings indicate that upper and lower airways represent interconnected but partially independent ecological niches where Achromobacter populations can diverge during colonization, supporting the view that both compartments contribute to their persistence and evolution in CF airways.
    Keywords:  Achromobacter; airway reservoir; antibiotic resistance; bacterial adaptation; cystic fibrosis; hypermutation; lung; virulence
    DOI:  https://doi.org/10.3390/pathogens15050452
  54. medRxiv. 2026 May 13. pii: 2026.05.08.26352758. [Epub ahead of print]
    Molecular Methods to Detect Vibrio cholerae and Associated Bacteriophages among Diarrheal Patients in Bangladesh.
    I Sriguha, M Mu, Abu Sayeed, E T Cato, A Creasy-Marrazzo, K Islam, I Ul Khabir, T R Bhuiyan, Y Begum, Taufiqul Islam, Zahid Hasan Khan, E Freeman, A Vustepalli, L Brinkley, D G Brown, D J Pouchnik, K Mi, Z Lin, J A Grembi, D T Leung, F Qadri, A I Khan, E J Nelson.
      Molecular diagnostics to detect Vibrio cholerae ( Vc ) may be negatively impacted by pathogen-specific lytic bacteriophage (phage) predation. To address this problem, phage detection as a proxy for pathogen detection has been proposed. However, efforts to modernize cholera diagnostics with molecular tools require addressing knowledge gaps on best practices to detect Vc and associated bacteriophages. We conducted polymerase chain reaction (PCR), quantitative PCR (qPCR), and nano-liter (nl) qPCR targeting Vc and known phages (ICP1/2/3) on stool samples collected from patients admitted at hospitals across Bangladesh. Of 4,975 patients enrolled, 2,574 diarrheal samples were collected and over 65,000 reactions were conducted, including replicates. We analyzed the results for target-specific assay alignment and then used machine learning to determine the effect of phage predation on Vc -assay alignment. Standard curve analyses were used to set qPCR-positivity thresholds at 7.3×10 5 CFU/mL for Vc and 1.7×10 3 , 9.3×10 3 , and 3.0×10 5 PFU/mL for ICP1, ICP2, and ICP3, respectively. Among 2,462 samples assayed by qPCR, target detection was 25.3% (623), 7.8% (193), 0.5% (13), and 5.8% (144) for Vc , ICP1, ICP2, and ICP3, respectively. There was strong alignment between assays for Vc detection (κ=0.785) and moderate alignment for phage detection (κ=0.609, 0.593, and 0.533 for ICP1/2/3, respectively). Phages were ranked as the first (ICP1) and third (ICP3) effectors of Vc diagnostic alignment. These findings provide insights on how to prioritize molecular methods in the cholera field as well as related less tractable diseases facing similar diagnostic challenges.
    IMPORTANCE: This paper presents a comprehensive comparison of molecular methods to detect Vibrio cholerae ( Vc ) and associated bacteriophage (phage) which can be used as a proxy for pathogen detection. This initiative is an important step towards modernizing cholera diagnostics with molecular tools. In this study, we found that quantitative polymerase chain reaction (qPCR) represents a reasonable approach to detect Vc and associated phages balancing assay performance, cost, and accessibility. A key additional finding was that phage predation was found to be a leading factor that impacts the alignment of molecular methods to detect Vc . While we recommend qPCR be added to the cholera diagnostic toolkit, the effects of phage predation need to be accounted for in the development and evaluation of cholera diagnostics. These findings have applicability to less tractable disease where diagnostics share similar vulnerabilities.
    DOI:  https://doi.org/10.64898/2026.05.08.26352758
  55. Infect Drug Resist. 2026 ;19 598824
    Root Cause Analysis for Outbreaks of Carbapenem-Resistant Acinetobacter baumannii and Pseudomonas aeruginosa in a Pediatric Intensive Care Unit: A Retrospective Study.
    Weijun Peng, Youhua Hao, Honghui Ding, Zhenling Wang, Kun Tan, Li Tan.
       Objective: Children in the pediatric intensive care unit (PICU) are inherently susceptible to multidrug-resistant (MDR) bacterial infections due to physiological vulnerabilities and clinical management-related factors. Such infections are prone to outbreaks and confer substantial harm. This study aims to investigate the etiologies of carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) infection outbreaks in the PICU and develop targeted prevention and control strategies using the root cause analysis (RCA) approach.
    Methods: A retrospective analysis was conducted on five cases (n=5) of MDR infection clusters admitted to the PICU of a large comprehensive hospital from January to February 2024. RCA was applied to identify underlying causes, develop targeted interventions, and evaluate their effectiveness.
    Results: From 31 January to 18 February 2024, four CRAB strains and three CRPA strains were detected among five patients (n = 5). Environmental sampling (145 specimens) revealed CRAB in four sites (crane tower, handwashing basin wall, healthcare workers' hands, and PDA devices) and CRPA in two sites (fiberoptic bronchoscopes and healthcare workers' hands). Post-intervention, no further MDR clusters were observed in 2024, indicating effective control.
    Conclusion: RCA facilitates systematic identification of root causes for MDR outbreaks, enabling targeted interventions to curb transmission and strengthen infection control practices.
    Keywords:  carbapenem-resistant Acinetobacter baumannii; carbapenem-resistant Pseudomonas aeruginosa; multidrug-resistant bacteria; outbreak; pediatric intensive care unit; root cause analysis
    DOI:  https://doi.org/10.2147/IDR.S598824
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