bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2025–09–28
fifty papers selected by
Luca Bolliger, lxBio
  1. Phage therapy: An international survey of attitudes and experiences amongst clinicians.
  2. Revolutionizing diabetic foot ulcer treatment: phage therapy as a next-generation antimicrobial approach- a review on breaking the cycle of resistance.
  3. Smart Phages: Leveraging Artificial Intelligence to Tackle Prosthetic Joint Infections.
  4. A pharmacometric model assessing the in vitro synergistic effect of a bacteriophage-polymyxin B combination in a clinical multidrug-resistant K. pneumoniae isolate.
  5. Isolation, purification, and phenotypic characterization of virulent Klebsiella pneumoniae phages from environmental samples in Addis Ababa, Ethiopia: A synergistic approach combining spot assay and streak plating.
  6. Prophage Activation: An In Silico Platform for Identifying Prophage Regulatory Elements to Inform Phage Engineering Against Drug-Resistant Bacteria.
  7. Development of an Acid-Protective Polymer Encapsulation Formulation for Oral Delivery of Salmonella Phages.
  8. Computational Pipeline for Targeted Integration and Variable Payload Expression in Bacteriophage Engineering.
  9. Interplay Between Bacterial Extracellular Vesicles and Phages: Receptors, Mechanisms, and Implications.
  10. In vitro and in vivo antibacterial efficacy of bacteriophage combined with tigecycline against carbapenem-resistant Klebsiella pneumoniae and characterization of phage resistant mutants.
  11. Rational design of a hospital-specific phage cocktail to treat Enterobacter cloacae complex infections.
  12. Application of three-dimensional bacteriophage cocktail biogel on infected burn wounds in rats.
  13. The Efficacy of Inhaled Phage Cocktail to Prevent Ventilator-Associated Pneumonia in Children: A Double-Blind Clinical Trial.
  14. Efficacy of bacteriophage cocktails administered through mucosal and non-mucosal routes for urinary tract infections caused by Enterobacter cloacae: A preclinical study.
  15. Review of the Arbitrium (ARM) System: Molecular Mechanisms, Ecological Impacts, and Applications in Phage-Host Communication.
  16. How to spare gut microbiota from antibiotic effects? PK-PD based innovative strategies, target specificity, and molecule-to-medicinal properties.
  17. A comprehensive review of advanced strategies to combat antimicrobial resistance.
  18. Adjunctive bacteriophage therapy for refractory / resistant Pseudomonas aeruginosa infections - Bottlenecks and proposed solutions.
  19. Advancing Antibacterial Strategies: CRISPR-Phage-Mediated Gene Therapy Targeting Bacterial Resistance Genes.
  20. Co-Occurrence of Toxic Bloom-Forming Cyanobacteria Planktothrix, Cyanophage, and Symbiotic Bacteria in Ohio Water Treatment Waste: Implications for Harmful Algal Bloom Management.
  21. CRISPR adaptation in Streptococcus thermophilus benefits from phage environmental DNA.
  22. From Pandemic to Resistance: Addressing Multidrug-Resistant Urinary Tract Infections in the Balkans.
  23. Phage Resistance Modulates Escherichia coli B Response to Metal-Based Antimicrobials.
  24. Picobirnavirus: how do you find where it's hiding?
  25. Gut microbiota therapy for chronic kidney disease.
  26. Prophage against phage.
  27. Micro/nanomotors for biofilm remediation: Nanoarchitectonic breakthroughs with a focus on regulatory and clinical translation challenges.
  28. Use of Oral Antibiotics for Diabetic Foot Osteomyelitis: A Systematic Review.
  29. Catheter-Associated Urinary Tract Infections: Understanding the Interplay Between Bacterial Biofilm and Antimicrobial Resistance.
  30. Global research landscape and advancements on the links between the gut microbiome and insulin resistance: hot issues, trends, future directions, and bibliometric analysis.
  31. Comparative analysis of phage cocktail activity against uropathogenic E. coli strains using spot overlay assay.
  32. Biofilms Exposed: Innovative Imaging and Therapeutic Platforms for Persistent Infections.
  33. Probiotics in IBD: Evidence and Perspectives on Patient Health and Disease Management.
  34. Biocompatible Metal Sulfide-Based Nanomaterials for Antimicrobial and Wound Healing Applications.
  35. Bacteriophage T4 propagation in E.coli exposed to severe substrate limitation.
  36. Biological Models for Evaluating Hydrogel-Based Formulations in Wound Healing.
  37. War impact on antimicrobial resistance and bacteriological profile of wound infections in Ukraine.
  38. Probiotic-Based Materials as Living Therapeutics.
  39. The respiratory tract virome: unravelling the role of viral dark matter in respiratory health and disease.
  40. Personalized aerosolised bacteriophage treatment of a pulmonary infection due to carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae in an infant.
  41. Artificial Intelligence in Skin and Wound Care: Enhancing Diagnosis and Treatment With Large Language Models.
  42. Advances in Novel Drug Delivery Systems: A Focus on Nanoparticles and Mucoadhesive Technologies.
  43. Characterization of new mouse models of acute and chronic Mycobacterium abscessus infection for antimicrobial drug screening.
  44. Confronting the Antimicrobial Resistance Crisis in China: Emerging Superbugs, Genomic Surveillance, and Innovative Countermeasures.
  45. SPAED: Harnessing AlphaFold Output for Accurate Segmentation of Phage Endolysin Domains.
  46. Medical Malpractice in Wound Care: A Multiple Case Series.
  47. An Overview of the Epidemiology of Multidrug Resistance and Bacterial Resistance Mechanisms: What Solutions Are Available? A Comprehensive Review.
  48. Isolation of Lytic Bacteriophages of Escherichia coli and Their Combined Use with Antibiotics Against the Causative Agents of Colibacillosis in Calves.
  49. Airway Microbiome in Children with Cystic Fibrosis: A Review of Microbial Shifts and Therapeutic Impacts.
  50. A Comprehensive Review of Pediatric Necrotizing Pneumonia.
  1. Int J Antimicrob Agents. 2025 Sep 19. pii: S0924-8579(25)00182-7. [Epub ahead of print] 107627
    Phage therapy: An international survey of attitudes and experiences amongst clinicians.
    Riley D Alvarez, Emma Cl Finlayson-Trick, Ruby Cy Lin, Greg J German.
      Phage therapy is a promising tool to combat the global threat of antimicrobial resistance. Clinicians, as part of interdisciplinary teams, play an integral role in identifying patients for therapy, delivering phages, and monitoring treatment outcomes and safety. As such, in the context of rapidly evolving regulatory landscapes, clinician insight is crucial for advancement of phage therapy. In this study, we describe the first published international anonymized survey aimed at identifying attitudes and experiences of clinicians and healthcare professionals towards phage therapy. We distributed the survey to participants in the Global Clinical Phage Rounds, a network of >300 phage clinicians, health professionals, and scientists, from October 15, 2024 - January 30, 2025. Thirty respondents representing North America, Europe, Oceania, Africa, and Asia completed the survey (response rate 9.6%). The majority of respondents were very well-informed about phage therapy and 93% would consider enrolling their patients in phage therapy randomized controlled trials. Respondents identified Pseudomonas aeruginosa, Klebsiella species, and Staphylococcus aureus as priority organisms and bone/joint, respiratory, and urinary tract infections as priority syndromes. Respondents had concerns about clinical use evidence, regulatory barriers, and accessing phage. Twenty respondents reported experience with phage therapy, so answered additional questions. These respondents acquired phages from sources like phage banks, industry, and importation from other countries. Respondents delivered phage therapy primarily in single-use cases via parenteral/intravenous, topical, or inhalation routes. Experienced respondents endorsed combinations of monitoring before, during, and/or after phage therapy. These results serve as a guiding initiative to improve phage therapy integration in healthcare.
    Keywords:  Antimicrobial resistance; Bacteriophage; Phage therapy; Prescribers Survey
    DOI:  https://doi.org/10.1016/j.ijantimicag.2025.107627
  2. J Diabetes Metab Disord. 2025 Dec;24(2): 205
    Revolutionizing diabetic foot ulcer treatment: phage therapy as a next-generation antimicrobial approach- a review on breaking the cycle of resistance.
    Sakshi Madaan, Ishwerpreet Kaur Jawanda, Kashish Madaan, Jasleen Kaur, Ridhi, Sharnya Pathak, Seema Kumari.
       Background: Diabetic foot ulcers (DFUs) are a major complication of diabetes, impacting approximately one-third of diabetic patients worldwide. Treating DFUs has become increasingly difficult due to the rise of multidrug-resistant bacteria like Staphylococcus aureus and Pseudomonas aeruginosa. These pathogens often form biofilms, which protect them from both antibiotics and the immune system, making infections harder to eliminate. As a result, new treatment approaches are urgently needed to overcome the limitations of traditional antibiotic therapies. This integrative review investigates the potential of bacteriophage (phage) therapy as an alternative treatment for DFUs. A thorough analysis of recent scientific literature was conducted to explore the underlying mechanisms of DFUs, the impact of antibiotic resistance and biofilms, and the biological properties of bacteriophages that make them effective against resistant infections. Key phage components-such as structural proteins, tail fibers, endolysins, and enzymes that degrade bacterial capsules-were examined for their therapeutic relevance.
    Results: Evidence from laboratory studies, animal models, and early clinical research shows that phage therapy is effective in targeting drug-resistant bacteria involved in DFUs. Phages offer several advantages, including their ability to specifically target harmful bacteria, break down biofilms, and multiply at infection sites. These characteristics make them a promising tool for treating chronic, non-healing wounds.
    Conclusion: Bacteriophage therapy represents a cutting-edge strategy for managing DFUs, particularly in cases where conventional antibiotics fail. By utilizing the natural antibacterial properties of phages, this approach could lead to more personalized and precise wound care, potentially transforming the way chronic diabetic ulcers are treated.
    Keywords:  Antibiotic resistance; Bacteriophage therapy; Biofilms; Diabetes; Diabetic foot ulcers (DFUs); Phage enzymes; Pseudomonas aeruginosa; Staphylococcus aureus
    DOI:  https://doi.org/10.1007/s40200-025-01736-z
  3. Antibiotics (Basel). 2025 Sep 19. pii: 949. [Epub ahead of print]14(9):
    Smart Phages: Leveraging Artificial Intelligence to Tackle Prosthetic Joint Infections.
    Nicita Mehta, Andrew T Nguyen, Edward K Rodriguez, Jason Young.
      Traditional antibiotic therapy has encountered significant challenges for clinical treatment of infections for multiple reasons, including antimicrobial resistance (AMR) and poor efficacy against biofilms, demanding research into alternative therapeutic agents. Because of their unique antimicrobial mechanisms as well as their target specificity, diversity, exponential self-amplification, and anti-biofilm activity, combined with recent advances in genomics and synthetic biology, bacteriophages have attracted increased interest as potential alternatives or therapeutic adjuncts to antibiotics. However, obstacles such as phage-host specificity, bacterial resistance, and the selection of optimal phages, amongst other factors, impede clinical adoption of phage therapy. Here, machine learning (ML) and artificial intelligence (AI) tools have the opportunity to revolutionize phage therapy by enhancing scalability, efficiency and precision of these therapies. This article highlights potential key applications of ML/AI in the study, development and deployment of phage therapy.
    Keywords:  artificial intelligence; bacteriophage; machine learning; phage therapy; prosthetic joint infection
    DOI:  https://doi.org/10.3390/antibiotics14090949
  4. Int J Antimicrob Agents. 2025 Sep 19. pii: S0924-8579(25)00183-9. [Epub ahead of print] 107628
    A pharmacometric model assessing the in vitro synergistic effect of a bacteriophage-polymyxin B combination in a clinical multidrug-resistant K. pneumoniae isolate.
    Aneeq Farooq, Sue C Nang, Heidi H Yu, Hasini Wickremasinghe, Mei-Ling Han, Yu-Wei Lin, Sebastian G Wicha, Jian Li.
       BACKGROUND: Klebsiella pneumoniae represents one of the most critical pathogens globally and bacteriophage (phage) therapy offers a promising alternative for treatment. Phage therapy poses challenges due to its high specificity and fast resistance development in bacteria. One promising option to overcome these challenges is combining phages with conventional antibiotics.
    OBJECTIVE: This study investigates phage kinetics and pharmacodynamic interactions between novel phage pK8 and polymyxin B against a clinical multidrug-resistant K. pneumoniae.
    METHODS: Time-kill assays with time-dissolved sampling of phages and bacteria were coupled with pharmacometric modelling to describe phage-bacteria kinetics and killing dynamics. Additionally, different interaction models were investigated to assess the observed synergy between phage pK8 and polymyxin B.
    RESULTS: Key findings reveal that while polymyxin B alone showed no effect and phage pK8 alone was not efficacious enough to prevent the regrowth of K. pneumoniae II-503, their combined application resulted in notable bactericidal effects up to complete eradication. This was particularly notable in scenarios with higher phage doses. The developed pharmacokinetic/pharmacodynamic model describes synergy as bacterial resensitization to polymyxin B when combined with phage pK8.
    CONCLUSIONS: The study shows that phage pK8 and polymyxin B combination effectively combats a clinical polymyxin-resistant K. pneumoniae strain. These promising results pave the way for further in vivo studies to validate and refine treatment strategies for tackling multidrug-resistant infections.
    Keywords:  Bacteriophage; Klebsiella pneumoniae; Pharmacodynamics; Pharmacokinetics; Polymyxin
    DOI:  https://doi.org/10.1016/j.ijantimicag.2025.107628
  5. PLoS One. 2025 ;20(9): e0331955
    Isolation, purification, and phenotypic characterization of virulent Klebsiella pneumoniae phages from environmental samples in Addis Ababa, Ethiopia: A synergistic approach combining spot assay and streak plating.
    Assefa Asnakew Abebe, Alemayehu Godana Birhanu, Tesfaye Sisay Tessema.
       BACKGROUND: Multidrug-resistant (MDR) Klebsiella pneumoniae poses a significant global health threat, necessitating alternative therapies like bacteriophage treatment. Traditional phage isolation methods, such as plaque assays, are resource-intensive and thus limit large-scale screening. This study aimed to isolate and purify phages targeting MDR K. pneumoniae using a combined spot-streak plating method and to compare its efficiency with conventional techniques.
    MATERIALS AND METHODS: A total of 62 environmental samples were screened against two MDR K. pneumoniae isolates using a combined approach: initial phage detection by spot assays followed by streak plate-based purification for isolating pure phage clones. Traditional plaque assays were also performed for comparison. Isolated phages were characterized by performing host range analysis against 45 bacterial isolates and determining their burst size. Additionally, their stability was assessed across various pH and temperature conditions, and single-step growth curve experiments were conducted.
    RESULTS: The combined spot assay and streak plate purification method yielded 22 phages, whereas plaque assays isolated 17 phages. Eight phages with high titers and lytic activity were selected for further analysis. These phages exhibited broad host ranges, with two phages lysing up to 55.5% of tested isolates. Stability assays showed effective lytic activity between pH 5 and 9 and temperatures up to 60°C. Single-step growth curves revealed latent periods ranging from 15 to 40 minutes and burst sizes between 76 and 310 PFU per infected cell. The combined method reduced both the isolation time and resource requirements.
    CONCLUSION: The integration of spot assays with streak plate-based purification provides an efficient and less resource-intensive method for isolating diverse phages targeting MDR K. pneumoniae. The isolated phages demonstrate promising broad-spectrum lytic activity and physiological stability, supporting their potential use in phage therapy.
    RECOMMENDATION: Further genomic characterization is necessary to confirm the strictly lytic nature of these phages and to exclude the presence of undesirable genes. Subsequent studies should focus on in vivo efficacy testing and formulation optimization to facilitate clinical application.
    DOI:  https://doi.org/10.1371/journal.pone.0331955
  6. Life (Basel). 2025 Sep 09. pii: 1417. [Epub ahead of print]15(9):
    Prophage Activation: An In Silico Platform for Identifying Prophage Regulatory Elements to Inform Phage Engineering Against Drug-Resistant Bacteria.
    Saher Musrrat, Zequan Han, Kai Wang, Yunhai Huang, Yanhui Xiang, Sen Liu, Wen Yin.
      Multidrug-resistant bacterial infections pose a severe global health threat, highlighting the urgent need for innovative therapeutic options beyond traditional antibiotics. Phage therapy, which employs bacteriophages to infect and eradicate pathogenic bacteria, specifically offers a promising solution. However, the lack of well-characterized therapeutic phages has limited their broader clinical use. A critical aspect of activating the lytic potential of dormant prophages involves the strategic manipulation of transcription factor binding sites (TFBS), which function as pivotal regulatory nodes governing the transition between lysogenic dormancy and lytic activation. Our platform utilizes advanced bioinformatics tools to accurately identify and analyze TFBS, facilitating the targeted redesign or replacement of these sites to disrupt host-mediated repression. By systematically simulating modifications of these regulatory 'switches,' our platform computationally predicts reduced repressor activity, suggesting the potential for prophage activation and bacterial cell lysis. This novel methodology not only broadens the spectrum of therapeutic bacteriophages but also establishes a basis for individualized phage-based therapies, presenting a robust strategy to address the escalating challenge of antibiotic-resistant infections. By enabling the precise identification and engineering of TFBS, our platform signifies a transformative advancement in phage biology, effectively bridging the divide between computational analysis and therapeutic application.
    Keywords:  bacteriophage engineering; lysogenic–lytic switch; multidrug-resistant bacteria; phage therapy; regulatory element editing
    DOI:  https://doi.org/10.3390/life15091417
  7. Viruses. 2025 Sep 02. pii: 1205. [Epub ahead of print]17(9):
    Development of an Acid-Protective Polymer Encapsulation Formulation for Oral Delivery of Salmonella Phages.
    Manju Bernela, Nitin Virmani, Bidhan Chand Bera, Rajesh Kumar Vaid, Medhavi Vashisth, Taruna Anand.
      Bacteriophage therapy can successfully provide additional treatment to control Salmonella infection, but low gastric pH limits its oral application. The present study aimed to develop an improved encapsulation formulation with enhanced acid protection for oral delivery of Salmonella phages using polymers. This was achieved by encapsulating a phage cocktail containing three different bacteriophages against Salmonella sp. in alginate beads incorporating polyvinyl alcohol (PVA), PVP-K30, and calcium carbonate as viscosity modifiers and acid protection enhancers. Further, the beads were coated with poly-L-lysine to improve the stability and tested for their efficacy for improved phage viability under in vitro acidic conditions for subsequent use in oral delivery. Moist beads were slimy, and semi-dried beads presented a coarse surface as observed using FE-SEM. In vitro studies revealed that the free phage cocktail exhibited complete inactivation when exposed to acidic pH 2.5 after 15 min incubation. In contrast, the encapsulated phage cocktail showed a decrease of only 1.66 log units in viability when incubated for 90 min at pH 2.5. Furthermore, oral delivery of the encapsulated phage cocktail in the poultry model significantly reduced bacterial load in infected birds' intestines.
    Keywords:  Salmonella; oral delivery system; phage; poultry
    DOI:  https://doi.org/10.3390/v17091205
  8. ACS Synth Biol. 2025 Sep 22.
    Computational Pipeline for Targeted Integration and Variable Payload Expression in Bacteriophage Engineering.
    Jonas Fernbach, Emese Hegedis, Martin J Loessner, Samuel Kilcher.
      Bacteriophages offer a promising alternative to conventional antimicrobials, especially when such treatments fail. While natural phages are viable for therapy, advances in synthetic biology allow precise genome modifications to enhance their therapeutic potential. One approach involves inserting antimicrobial genetic payloads into the phage genome. These are typically placed behind late-expressed genes, such as the major capsid gene (cps). However, phages engineered with toxic payloads often fail to produce viable progeny due to premature host shutdown. To broaden the scope of viable genetic insertion sites, we developed a method to identify intergenic loci with favorable expression profiles using the machine learning-based promoter prediction tool, PhagePromoter. Guided by these predictions, we designed a computationally assisted engineering pipeline for targeted genomic payload integration. We validated this approach by engineering bioluminescent reporter genes into the genome of the strictly lytic Staphylococcus phage K at various predicted loci. Using homologous recombination, we generated three recombinant phages, each carrying the reporter at a distinct genomic location. These engineered phages exhibited expression levels consistent with computational predictions and demonstrated temporal expression patterns corresponding to early, middle, or late gene clusters. Our study highlights the power of combining computational tools with classical genome analysis to streamline phage engineering. This method supports rational design and enables high-throughput, automated phage modification, advancing the development of personalized phage therapy.
    Keywords:  expression prediction; genetic engineering; machine learning; phage engineering; phage therapy; promoter prediction
    DOI:  https://doi.org/10.1021/acssynbio.5c00450
  9. Viruses. 2025 Aug 29. pii: 1180. [Epub ahead of print]17(9):
    Interplay Between Bacterial Extracellular Vesicles and Phages: Receptors, Mechanisms, and Implications.
    Angelika Bołoz, Valérie Lannoy, Tomasz Olszak, Zuzanna Drulis-Kawa, Daria Augustyniak.
      Bacteria and phages have coexisted for billions of years engaging in continuous evolutionary arms races that drive reciprocal adaptations and resistance mechanisms. Among the diverse antiviral strategies developed by bacteria, modification or masking phage receptors as well as their physical removal via extracellular vesicles are the first line of defense. These vesicles play a pivotal role in bacterial survival by mitigating the effects of various environmental threats, including predation by bacteriophages. The secretion of extracellular vesicles represents a highly conserved evolutionary trait observed across all domains of life. Bacterial extracellular vesicles (BEVs) are generated by a wide variety of Gram (+), Gram (-), and atypical bacteria, occurring under both natural and stress conditions, including phage infection. This review addresses the multifaceted role of BEVs in modulating bacteria-phage interactions, considering the interplay from both bacterial and phage perspectives. We focus on the dual function of BEVs as both defensive agents that inhibit phage infection and as potential facilitators that may inadvertently enhance bacterial susceptibility to phages. Furthermore, we discuss how bacteriophages can influence BEV production, affecting both the quantity and molecular composition of vesicles. Finally, we provide an overview of the ecological relevance and efficacy of BEV-phage interplay across diverse environments and microbial ecosystems.
    Keywords:  atypical bacteria; bacterial extracellular vesicles (BEVs); bacteriophages; membrane vesicles (MVs); outer membrane vesicles (OMVs); phage receptors; phage-bacteria interplay
    DOI:  https://doi.org/10.3390/v17091180
  10. Front Cell Infect Microbiol. 2025 ;15 1610625
    In vitro and in vivo antibacterial efficacy of bacteriophage combined with tigecycline against carbapenem-resistant Klebsiella pneumoniae and characterization of phage resistant mutants.
    Rui Zhu, Ruilin Wang, Bing Fei, Ruici Lu, Xiaojuan You, Xinwei Liu, Chunxia Wang, Yongwei Li.
      Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged as a critical global public health threat, characterized by high infection rates, elevated mortality, and limited therapeutic options. In this study, we isolated and characterized a novel bacteriophage (phage), designated as HZJ31, which exhibited potent lytic activity against CRKP strains. Phylogenetic and genomic analyses revealed that phage HZJ31 belongs to the order Caudovirales and lacks virulence factors, antibiotic resistance genes, and lysogeny-related elements, supporting its suitability for therapeutic applications. Phage HZJ31 exhibits remarkable anti-biofilm activity by preventing biofilm formation and disrupting established biofilms, with bacterial reduction rates exceeding 70% (P<0.05). In combination with Tigecycline, it significantly enhanced bactericidal efficacy, delayed the emergence of phage resistant mutants, and improved survival rates in Galleria mellonella larvae infection models. Compared to the bacterial-infected group, which had 80% larval mortality at 96 h, treatment with HZJ31 or TGC alone led to 50% and 60% survival, while their combination improved survival to 70% (P < 0.05). Notably, the phage-resistant mutant, which emerged due to capsule loss, resulted in reduced growth and virulence, while regaining sensitivity to certain antibiotics (such as gentamicin), indicating a fitness cost associated with phage resistance. Collectively, these findings provide valuable insights into phage-antibiotic synergy and underscore the promising clinical potential of phage HZJ31 as a therapeutic agent against CRKP infections.
    Keywords:  Galleria mellonella infection model; biofilm; carbapenem-resistant Klebsiella pneumoniae; phage resistance; phage therapy
    DOI:  https://doi.org/10.3389/fcimb.2025.1610625
  11. Nat Microbiol. 2025 Sep 24.
    Rational design of a hospital-specific phage cocktail to treat Enterobacter cloacae complex infections.
    Dinesh Subedi, Fernando Gordillo Altamirano, Rylee Deehan, Avindya Perera, Ruzeen Patwa, Xenia Kostoulias, Denis Korneev, Luke Blakeway, Nenad Macesic, Anton Y Peleg, Jeremy J Barr.
      The Alfred Hospital in Melbourne, Australia, has reported an ongoing outbreak of infections caused by multidrug-resistant Enterobacter cloacae complex (ECC). Phage therapy is a promising strategy to treat antimicrobial-resistant infections. Utilizing the hospital's isolate collection, built over the past decade, we established an initial 3-phage cocktail with 54% ECC coverage. We then iteratively improved this product by enhancing phage killing efficiency using phage adaptation and expanded host range through targeted phage isolation against low-coverage ECC isolates. This optimization yielded Entelli-02, containing five well-characterized virulent phages that target clinical ECC isolates via distinct bacterial cell surface receptors. Entelli-02 exhibits 88% host coverage against The Alfred Hospital's ECC isolate collection (n = 206), confirmed by plaque formation and reduced bacterial load in septicaemic mice by >99%. We produced this cocktail as a therapeutic-grade product, ready for clinical use. Entelli-02 represents a hospital-specific phage cocktail with frontline efficacy and on-demand availability.
    DOI:  https://doi.org/10.1038/s41564-025-02130-4
  12. Eur J Clin Microbiol Infect Dis. 2025 Sep 23.
    Application of three-dimensional bacteriophage cocktail biogel on infected burn wounds in rats.
    Elif Aydin, A Kocak Sezgin, M Koldemir Gunduz, G Kaymak, B Açikgoz, F Aslan, S Ali, A Karaynir, B Bozdoğan.
      Burn wound infections significantly hinder the healing process by disrupting the immune response and limiting treatment options due to increasing antibiotic resistance. In this study, the antimicrobial and tissue regeneration effects of a three-dimensional bacteriophage cocktail bio-gel were evaluated in vivo in burn wounds infected with antibiotic-resistant Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. Using an experimental burn model in Sprague Dawley rats, the effects of phage bio-gel treatment on inflammatory response, cellular repair mechanisms, and wound closure dynamics were analyzed through molecular, biochemical, and histopathological assessments. Application of the bacteriophage bio-gel significantly accelerated wound healing in infected burn groups, with healing rates ranging from 77.56 to 89.75% on days 15 and 20. Cytokine analysis demonstrated that phage therapy modulated inflammation by reducing IL-1β, IL-6, and TNF-α levels (p < 0.05). Molecular analyses examining extracellular matrix dynamics showed a significant increase in TGF-β1, Smad-2/3, and collagen type 1 gene expression, indicating enhanced fibroblast activation and tissue remodeling. While MMP-2 and hydroxyproline levels increased, MMP-9 levels decreased following phage treatment. Histopathological evaluations revealed that re-epithelialization and tissue remodeling were accelerated, while inflammation was reduced in the A. baumannii and K. pneumoniae infected groups. These findings suggest that bacteriophage-based bio-gels provide a promising alternative for treating polymicrobial burn wound infections. The results indicate that bacteriophage biomaterials exhibit superior wound healing potential compared to conventional treatments, particularly in infections caused by antibiotic-resistant pathogens.
    Keywords:  Antimicrobial; Bacteriophage; Burn wound; MMP-2; MMP-9; Smad2/3
    DOI:  https://doi.org/10.1007/s10096-025-05269-4
  13. Biomedicines. 2025 Aug 29. pii: 2103. [Epub ahead of print]13(9):
    The Efficacy of Inhaled Phage Cocktail to Prevent Ventilator-Associated Pneumonia in Children: A Double-Blind Clinical Trial.
    Mohammad Reza Navaeifar, Golnar Rahimzadeh, Raha Rezai, Hormoz Ranjbar, Kofi Asare-Addo, Ali Nokhodchi, Mohammad Sadegh Rezai.
      Background/Objectives: Phage therapy is gaining attention as a potential alternative to antibiotics. This study investigates the potential use of a phage cocktail as a preventive measure against ventilator-associated pneumonia (VAP) in children. Methods: Sixty patients were selected from the pediatric intensive care units for this double-blind clinical trial. The inclusion criteria involved patients requiring invasive mechanical ventilation for more than two days. This, however, excluded newborns and children with bacterial pneumonia. The intervention group received the standard country protocol drugs in addition to 5 mL of phage cocktail suspension administered every 24 h through an in-line mesh nebulizer for 7 days. The two groups were compared in terms of the incidence of VAP, survival rate, and duration of hospitalization. Results: The intervention with phages had a significant impact on reducing the occurrence of VAP compared to the group receiving a placebo. The data showed that there was a significant difference in the occurrence of VAP between the two groups, with a lower percentage of VAP in the phage cocktail group (p < 0.05). Additionally, the cultures of specific bacterial strains did not yield positive results. Notably, there were no significant differences between the intervention and placebo groups in terms of mortality rates and duration of hospitalization (p > 0.05). Conclusions: Inhalation of a phage cocktail shows a promising effect in preventing VAP in PICU patients at a tertiary hospital in Iran with no observed side effects. However, further, larger clinical trials are necessary to validate its efficacy.
    Keywords:  children; inhalation; phage cocktail; ventilator-associated pneumonia (VAP)
    DOI:  https://doi.org/10.3390/biomedicines13092103
  14. Microb Pathog. 2025 Sep 18. pii: S0882-4010(25)00749-1. [Epub ahead of print]209 108024
    Efficacy of bacteriophage cocktails administered through mucosal and non-mucosal routes for urinary tract infections caused by Enterobacter cloacae: A preclinical study.
    Srishti Singh, Alok Kumar Singh, Alakh Narayan Singh, Sudhir Kumar Singh, Virendra Bahadur Yadav, Mayank Gangwar, Minakshi Sahu, Deepak Kumar, Gopal Nath.
      This preclinical study assessed the effectiveness of a phage cocktail in completely curing Enterobacter cloacae-associated urinary tract infections (UTIs) in a mouse model, employing various routes and dosages (both in quantity and frequency). Three lytic phages, designated ΦENT1, ΦENT2, and ΦENT3, were identified and characterised phenotypically using transmission electron microscopy (TEM) and genotypically through ERIC and restriction enzyme analysis. To induce a UTI, ten groups of female Swiss albino mice were inoculated with 100 μL containing 1 × 109 CFU/mL via the urethral route with E. cloacae GNENT11213. The mice were subsequently treated with the phage cocktail via subcutaneous, oral, transurethral, and rectal routes. The efficacy of these routes was optimised at two doses of phages, namely 1 × 109 PFU/mL (5 mice) and 1 × 105 PFU/mL (5 mice). Furthermore, the levels of Endotoxins and Interleukin-6 (IL-6) were measured to assess the negative impact of phage therapy. Our findings indicated that E. cloacae GNENT11213 could be effectively eliminated with one dosage of 1 × 109 Plaque-Forming Units per mouse (PFU/mouse) and two doses of the phage cocktail containing 1 × 105 PFU/mouse administered through the urethra (local mucosa). Interestingly, higher concentrations of phage particles and multiple doses were necessary for other mucosal routes, such as oral and rectal administration, to effectively eradicate E. cloacae GNENT11213 at any stage of acute illness UTI. Furthermore, phage treatment did not significantly alter the levels of IL-6 and Endotoxins. Non-mucosal routes, such as subcutaneous, were ineffective in curing the infection.
    Keywords:  Enterobacter cloacae; Mucosal and nonmucosal routes; Phage cocktail
    DOI:  https://doi.org/10.1016/j.micpath.2025.108024
  15. Microorganisms. 2025 Sep 04. pii: 2058. [Epub ahead of print]13(9):
    Review of the Arbitrium (ARM) System: Molecular Mechanisms, Ecological Impacts, and Applications in Phage-Host Communication.
    Junjie Shang, Qian Zhou, Yunlin Wei.
      Bacteriophages (phages) play a pivotal role in shaping microbial communities and driving bacterial evolution. Among the diverse mechanisms governing phage-host interactions, the Arbitrium (ARM) communication system represents a recently discovered paradigm in phage decision-making between the lytic and lysogenic cycles. Initially identified in Bacillus-infecting phages, the ARM system employs a quorum-sensing-like peptide signaling mechanism to modulate infection dynamics and optimize population-level survival strategies. Recent studies have elucidated the structural and functional basis of ARM regulation, highlighting its potential applications in antimicrobial therapy, microbiome engineering, and synthetic biology. The significance of ARM systems lies in their ability to regulate bacterial population stability and influence the evolutionary trajectories of microbial ecosystems. Despite being a relatively recent discovery, ARM systems have garnered considerable attention due to their role in decoding phage population dynamics at the molecular level and their promising biotechnological applications. This review synthesizes current advancements in understanding ARM systems, including their molecular mechanisms, ecological implications, and translational potential. By integrating recent findings, we provide a comprehensive framework to guide future research on phage-host communication and its potential for innovative therapeutic strategies.
    Keywords:  arbitrium system; bacteriophages; phage–host communication; quorum-sensing
    DOI:  https://doi.org/10.3390/microorganisms13092058
  16. RSC Med Chem. 2025 Sep 03.
    How to spare gut microbiota from antibiotic effects? PK-PD based innovative strategies, target specificity, and molecule-to-medicinal properties.
    Abhishek Rai, Vaishnavi Newaskar, Nibedita Roy, Sankar K Guchhait.
      Conventional broad-spectrum antibiotics often disrupt gut microbiota, causing a range of health issues like inflammatory bowel disease (IBD), secondary infections, colorectal cancer, liver disease, cognitive impairment, diabetes, and obesity. While the 'one drug treats all' strategy offers convenience, the long-term consequences of microbiota imbalance caused by such antibiotics can no longer be ignored. Modern antibiotic discovery and development programs must consider the strategies that minimize microbiota disruption to prevent long-term dysbiosis. This article presents, for the first time, a critical analysis of emerging microbiota-sparing pharmacokinetic-pharmacodynamic (PK-PD) based innovative antibacterial therapeutic strategies, such as transporter (BmpD)-mediated selective uptake, selective accumulation driven by efflux deficiency, pathogen-specific and pH-dependent selective cellular absorption, adjuvant facilitated therapy, β-lactamase-directed selectivity, microbiota-conserving immunotherapy, and CRISPR-based phage therapy. It highlights target-specific antibacterial approaches aimed at distinct bacterial pathways, such as lipoprotein transport, fatty acid biosynthesis, protein biosynthesis via methionyl-tRNA synthetase (MetRS), and DNA replication through DNA polymerase IIIC, which can minimize microbiota disruption and antibiotic-associated dysbiosis. Additionally, the discovery of antibacterial clinical candidates, such as afabicin, lolamicin, hygromycin A, cadazolid, and ribaxamase, that exhibit pathogen-specific efficacy with limited gut exposure, has been discussed with an in-depth analysis of their mechanism of actions (MoAs) and specific bacterial targets, molecular structure-to-medicinal insights, and strategic innovations. Collectively, this article provides a perspective for next generation antibacterial drug design and discovery, focusing on innovative strategies, specific biological pathways, and key molecular features that spare gut microbiota while maximizing antibacterial treatment efficacy.
    DOI:  https://doi.org/10.1039/d5md00591d
  17. Arch Microbiol. 2025 Sep 26. 207(11): 281
    A comprehensive review of advanced strategies to combat antimicrobial resistance.
    Bikramaditya Behera, Rajrattan Singh, Komal Sharma, Ansh Rai, Shreya Singh, Biji Balan.
      Antimicrobial Resistance (AMR) is a growing global issue, as many first-line antibiotics are becoming less effective due to their overuse and misuse. Recent advances in novel antibiotic derivatives reveal mechanisms designed to counteract AMR. Even though conventional antimicrobial therapy has failed, no new antibiotic class has been developed in the past decade. Consequently, various innovative alternative tactics have been discovered to counteract drug-resistant pathogens. The article reviews novel approaches in combating AMR, which include antimicrobial peptides, phage therapy, CRISPR-Cas gene editing, nanomaterial-based antimicrobials, immunomodulatory agents, innovative physicochemical strategies, and combination therapy. Collectively, these approaches utilize cutting edge technologies that mark a shift from the traditional paradigm of antibiotics to integrated next-generation therapeutics. AMR remains a serious issue despite all of the noted advancements, and hence, a collaborative and multidisciplinary action involving researchers, healthcare professionals, policymakers, and pharmaceutical sector is urgently required. The emergence and burden of AMR can be better tackled by inventiveness, cooperation, and proactive approaches.
    Keywords:  Antimicrobial peptides (AMPs); Antimicrobial resistance (AMR); CRISPR cas system; Multi-drug resistant (MDR); Nanoparticles
    DOI:  https://doi.org/10.1007/s00203-025-04464-3
  18. Int J Antimicrob Agents. 2025 Sep 18. pii: S0924-8579(25)00184-0. [Epub ahead of print] 107629
    Adjunctive bacteriophage therapy for refractory / resistant Pseudomonas aeruginosa infections - Bottlenecks and proposed solutions.
    Shimin Jasmine Chung, Shuhua Thong, Dorothy Hui Ling Ng, Lester Jun Long Wong, Tse Hua Nicholas Wong, Tan Thuan Tong, Tan Ban Hock, Andrea Lay-Hoon Kwa.
      
    Keywords:  Bacteriophage therapy, Pseudomonas aeruginosa, refractory; resistant infections, antibiotic potency, phage access
    DOI:  https://doi.org/10.1016/j.ijantimicag.2025.107629
  19. Curr Gene Ther. 2025 Sep 19.
    Advancing Antibacterial Strategies: CRISPR-Phage-Mediated Gene Therapy Targeting Bacterial Resistance Genes.
    Arvind Kumar Patel, Neha Singh, Neetu Sachan, Phool Chandra.
      One of the most significant issues facing the world today is antibiotic resistance, which makes it increasingly difficult to treat bacterial infections. Regular antibiotics no longer work against many bacteria, affecting millions of people. A novel approach known as CRISPR-phage therapy may be beneficial. This technique introduces a technology called CRISPR into resistant bacteria using bacteriophages. The genes that cause bacteria to become resistant to antibiotics can be identified and cut using CRISPR. This enables antibiotics to function by inhibiting the bacteria. This approach is highly precise, unlike conventional antibiotics, so it doesn't damage our bodies' beneficial bacteria. Preliminary studies and limited clinical trials suggest that this technique can effectively target drug-resistant bacteria such as Klebsiella pneumoniae and Methicillinresistant Staphylococcus aureus (MRSA). However, challenges in phage engineering, host delivery, and the growing threat of bacterial CRISPR resistance demand urgent and strategic innovation. Our perspective underscores that without proactive resolution of these hurdles, the current hopefulness could disappear. Looking ahead, integrating next-generation Cas effectors, non-DSB editors, and resistance monitoring frameworks could transform CRISPR-phage systems from an experimental novelty into a clinical mainstay. This shift will require not only scientific ingenuity but also coordinated advances in regulatory, translational, and manufacturing efforts.
    Keywords:  Antibacterial resistant; CRISPR-phage therapy; gene editing; precision medicine.
    DOI:  https://doi.org/10.2174/0115665232417037250916112841
  20. Toxins (Basel). 2025 Sep 05. pii: 450. [Epub ahead of print]17(9):
    Co-Occurrence of Toxic Bloom-Forming Cyanobacteria Planktothrix, Cyanophage, and Symbiotic Bacteria in Ohio Water Treatment Waste: Implications for Harmful Algal Bloom Management.
    Angela Brooke Davis, Morgan Evans, Katelyn McKindles, Jiyoung Lee.
      Cyanobacterial blooms are increasingly becoming more intense and frequent, posing a public health threat globally. Drinking water treatment plants that rely on algal bloom-affected waters may create waste (water treatment residuals, WTRs) that concentrates contaminants. Source waters may contain harmful cyanobacteria, cyanophages (bacteriophages that infect cyanobacteria), and bacteria. Cyanophages are known to affect bloom formation and growth dynamics, so there is a need to understand viral-host dynamics between phage and bacteria in these ecosystems for managing cyanobacteria. This study isolated and characterized lytic cyanophages from WTRs of a HAB-affected lake in Ohio that infect toxic bloom-forming filamentous cyanobacteria Planktothrix agardhii. Phage infections in the Lake Erie cyanobacteria culture were examined visually and via microscopy and fluorometry. Whole genome sequencing and metagenomic analyses were also conducted. Observed changes in Planktothrix included sheared and shriveled filaments, reduced clumping, and buoyancy changes. Photosynthetic pigmentation was unexpectedly more apparent during phage infection. Metagenomic analyses identified nineteen phages and seven other co-existing bacterial genera. Annotated bacterial genomes contained metabolic pathways that may influence phage infection efficiency. Viral genomes were successfully tied to microbial hosts, and annotations identified important viral infection proteins. This study examines cyanobacterial-phage interactions that may have potential for bioremedial applications.
    Keywords:  Planktothrix agardhii; bioremediation; cyanophages; lake erie; microcosm; water treatment residuals
    DOI:  https://doi.org/10.3390/toxins17090450
  21. mSphere. 2025 Sep 22. e0045325
    CRISPR adaptation in Streptococcus thermophilus benefits from phage environmental DNA.
    F R Croteau, J Tran, A P Hynes.
      The CRISPR-Cas system is a bacterial adaptive immune system that protects against infection by phages: viruses that infect bacteria. To develop immunity, bacteria integrate spacers-fragments of the invading nucleic acids-into their CRISPR array to serve as the basis for sequence-targeted DNA cleavage. However, upon infection, a phage quickly takes over the metabolism of the bacterium, leaving little time for the bacterium to acquire new spacers, transcribe them, and use them to cut the invading DNA. To develop CRISPR immunity, bacteria must be safely exposed to phage DNA. Phage infection releases environmental DNA (eDNA) which could be involved in the development of CRISPR immunity. Using Streptococcus thermophilus and phages 2972 and 858 as a model for CRISPR immunity, we show that eDNA is involved in CRISPR immunity, as generation of phage-immune bacterial colonies decreases with eDNA digestion. Furthermore, it is phage eDNA specifically that impacts CRISPR immunity since only its addition increases the generation of phage-immune colonies. We also show that the effect of eDNA is phage-specific, sequence-specific, and can even be traced to a region of the genome covering the early-expressed genes, which differ between phages 2972 and 858. However, we also show that eDNA is not used as a source of genetic information for spacer acquisition. These results link eDNA to the CRISPR-Cas system, providing a better understanding of the context of the emergence of CRISPR immunity and could inform our understanding of the mechanisms through which bacteria detect phage infection.IMPORTANCEHow can a bacterial adaptive immune system (the CRISPR-Cas system) exist at all, when exposure to a virulent phage is so consistently lethal? We proposed that bacteria might actively sample their genetic environment for phage DNA through natural competence. In testing this hypothesis, we revealed that free phage DNA is important to CRISPR immunity-but not as the source of the immunological memory.
    Keywords:  CRISPR-Cas; adaptive immunity; bacteriophage; eDNA; environmental DNA; natural competence; phage resistance
    DOI:  https://doi.org/10.1128/msphere.00453-25
  22. Antibiotics (Basel). 2025 Aug 22. pii: 849. [Epub ahead of print]14(9):
    From Pandemic to Resistance: Addressing Multidrug-Resistant Urinary Tract Infections in the Balkans.
    Rumen Filev, Boris Bogov, Mila Lyubomirova, Lionel Rostaing.
      Background/Objectives: The rise in urinary tract infections caused by multidrug-resistant (MDR) bacteria presents a serious public health challenge across the Balkans, a region already burdened by aging populations, healthcare resource limitations, and fragmented antimicrobial surveillance systems. Methods: This review explores the epidemiology, risk factors, and consequences of MDR UTIs, particularly in the context of the COVID-19 pandemic, which significantly accelerated antimicrobial resistance (AMR) due to widespread, inappropriate antibiotic use. Results: The paper discusses region-specific data on resistance trends, highlights the gaps in diagnostic infrastructure, and evaluates emerging clinical strategies including antimicrobial stewardship (AMS), rapid diagnostic technologies, novel antibiotics, and non-antibiotic alternatives such as bacteriophage therapy and vaccines. Conclusions: Policy recommendations are provided to strengthen surveillance, promote evidence-based treatment, and ensure equitable access to diagnostic and therapeutic tools. A multidimensional and regionally coordinated response is essential to curb the MDR UTI burden and safeguard public health across the Balkans.
    Keywords:  Balkans; COVID-19 pandemic; antimicrobial resistance (AMR); health policy; multidrug-resistant urinary tract infections (MDR UTIs)
    DOI:  https://doi.org/10.3390/antibiotics14090849
  23. Antibiotics (Basel). 2025 Sep 18. pii: 942. [Epub ahead of print]14(9):
    Phage Resistance Modulates Escherichia coli B Response to Metal-Based Antimicrobials.
    Franklin C Ezeanowai, Akamu J Ewunkem, Ugonna C Morikwe, Larisa C Kiki, Lindsey W McGee, Joseph L Graves, Liesl K Jeffers-Francis.
      Background/Objective: The rise of multidrug-resistant bacteria underscores the urgent need for alternative antimicrobial strategies. Metal-based compounds and bacteriophage (phage) therapy have emerged as promising candidates, but the evolutionary trade-offs associated with these selective pressures and their combination remain poorly understood. This study aimed to investigate how prior exposure to T4 phage influences Escherichia coli B's subsequent adaptation to iron (III) stress and to assess the resulting phenotypic and genomic signatures of dual resistance. Method: In this study, we performed experimental evolution using Escherichia coli B to investigate adaptive responses under four conditions: control (LB broth), T4 phage-only, iron (III) sulfate-only, and sequential phage followed by iron (III) exposure. Each treatment consisted of ten independently evolved populations (biological replicates), all derived from a common ancestral strain and passaged daily for 35 days. Phage resistance evolved rapidly, with complete resistance observed within 24 h of exposure. Results: In contrast, iron-selected populations evolved tolerance to high iron concentrations (1000-1750 mg/L) over time at a cost to resistance in other metals (gallium and iron (II) and antibiotics (tetracycline). Notably, prior phage exposure altered these outcomes: phage/iron-selected populations retained phage resistance and iron tolerance but showed diminished resistance to iron (II) and distinct antibiotic sensitivity profiles. Whole-genome sequencing revealed stressor-specific adaptations: large deletions in phage receptor-related genes (waaA and waaG) under phage pressure, and selective sweeps in iron-adapted populations affecting regulatory and membrane-associated genes (qseB, basR, aroK, fieF, rseB, and cpxP). Conclusions: These results demonstrate that the sequence of environmental stressors significantly shapes phenotypic and genetic resistance outcomes. Our findings highlight the importance of fitness epistasis and historical contingency in microbial adaptation, with implications for the design of evolution-informed combination therapies.
    Keywords:  Escherichia coli B; Iron (III); T4 phage; antimicrobial resistance; experimental evolution; genomic adaptation; heavy metals
    DOI:  https://doi.org/10.3390/antibiotics14090942
  24. Crit Rev Microbiol. 2025 Sep 20. 1-11
    Picobirnavirus: how do you find where it's hiding?
    Abbey L K Hutton, Susanna Grigson, Louise Bartle, Bhavya Papudeshi, Vijini Mallawaarachchi, Anita Tarasenko, James G Mitchell, Robert A Edwards.
      Picobirnaviruses (PBVs) are double-stranded RNA viruses detected in various environments and host-associated samples, including those from humans, non-human animals, invertebrates and birds. First described in human fecal material, PBVs were initially hypothesized to be human enteric pathogens. However, no definitive association with disease has been established. Their pathogenic potential remains unclear, therefore, their presence in clinical or environmental samples may reflect asymptomatic colonization, indirect association or infection of a non-human host. The PBV genome exhibits remarkably high genetic diversity both within and across its genomic segments, as well as notable variability in genetic code usage. Some PBV genomes use alternative codon assignments, raising the possibility that they infect prokaryotic or otherwise unconventional hosts. This review critically examines the experimental and bioinformatic methods used to detect PBVs and infer their host range. We distinguish between methods used for PBV genome identification (e.g. PCR, metagenomic sequencing) and those aimed at host determination (e.g. culturing attempts, codon usage bias, cloning into model systems). We also evaluate the challenges and limitations associated with each approach. Elucidating PBVs' host range is essential to understanding their biological roles and ecological significance, including potential implications for human and animal health and microbial community dynamics across ecosystems.
    Keywords:  PCR; Picobirnavirus; RdRp; bacteriophages; metagenomic sequencing
    DOI:  https://doi.org/10.1080/1040841X.2025.2560918
  25. Front Immunol. 2025 ;16 1660226
    Gut microbiota therapy for chronic kidney disease.
    Chunguang Liu, Junhong Wang, Lei Lei, Liping Li, Xingxing Yuan.
      Chronic kidney disease (CKD), affecting 13% of the global population, is increasingly linked to gut microbiota dysbiosis, a condition driven by uremic toxins accumulation, metabolic alterations, and dietary factors. This mini review explores gut microbiota modulation as a therapeutic strategy to alleviate CKD symptoms, focusing on interventions that target gut microbiota composition and function. Prebiotics, such as resistant starch, have been shown to lower uremic toxins and reduce inflammation, while dietary adjustments, including low-protein and gluten-free diets, modulate microbial diversity and improve renal biomarkers. Fecal microbiota transplantation (FMT), which stabilizes creatinine levels and shifts gut microbiota toward beneficial taxa, represents another promising approach. However, limitations persist: synbiotics, which often induce gut microbiota shifts, frequently lack clinical impact; probiotics, which enhance glucose control and oxidative stress mitigation, exhibit variable efficacy; and interventions such as propolis or cranberry extract, which have been tested, prove ineffective. The causal relationship between gut microbiota dysbiosis and CKD progression, which remains unclear, is further complicated by methodological heterogeneity across studies. Emerging strategies, including phage therapy and artificial intelligence-driven multi-omics integration, which hold significant promise, require further validation. Future research must prioritize longitudinal studies, maternal gut microbiota optimization, and personalized approaches, which are essential for advancing CKD management. While gut microbiota modulations hold therapeutic potential, translating these findings into clinical practice demands rigorous trials to address inconsistencies and establish mechanistic links, ultimately shifting CKD management from reactive treatment to precision-based prevention.
    Keywords:  chronic kidney disease; fecal microbiota transplantation; gut microbiota; precision-based prevention; therapeutic interventions
    DOI:  https://doi.org/10.3389/fimmu.2025.1660226
  26. Nat Rev Microbiol. 2025 Sep 24.
    Prophage against phage.
    Andrea Du Toit.
      
    DOI:  https://doi.org/10.1038/s41579-025-01246-y
  27. Biomaterials. 2025 Sep 13. pii: S0142-9612(25)00634-9. [Epub ahead of print]326 123715
    Micro/nanomotors for biofilm remediation: Nanoarchitectonic breakthroughs with a focus on regulatory and clinical translation challenges.
    Tijana Maric, Yuya Tanaka, Ziqiao Li, Jing Wu, Jialing Li, Jianguo Guan, Anja Boisen.
      Biofilm-associated bacterial infections, notorious for their resistance to standard therapies, pose a critical challenge in clinical practice. Micro and nanomotors (MNMs) have emerged as dynamic tools capable of penetrating biofilm matrices and enabling targeted antimicrobial delivery through autonomous motion. Recent advances in nanoarchitectonic design, spanning fuel-free or chemical propulsion, biohybrid systems, and multimodal actuation, significantly enhance their therapeutic precision and biocompatibility. This review critically examines the evolution of MNM materials, geometries, and designs, emphasizing their mechanical disruption of extracellular polymeric substances and synergistic bactericidal effects. Innovations such as cascade-driven MNMs and stimuli-responsive platforms demonstrate >90 % biofilm eradication in vitro and accelerated wound healing in vivo. What distinguishes this review from existing literature is its integrated focus on regulatory and translational barriers to clinical adoption, an aspect seldom addressed in prior MNM reviews. In addition to advances in materials and design, we discuss challenges that must be overcome for clinical translation, including long-term biosafety, degradation, scalable manufacturing under Good Manufacturing Practice (GMP), and regulatory ambiguities surrounding nanoscale medical devices. We outline a path forward for addressing these barriers by emphasizing the need for standardized toxicity testing, stronger interdisciplinary collaboration, and the use of emerging regulatory tools such as Safe(r) Innovation Approaches (SIA), the EU's Safe and Sustainable by Design (SSbD) initiative, and regulatory sandboxes to help accelerate clinical translation. By integrating material and design innovation with regulatory foresight, MNM technology holds transformative potential for combating antibiotic-resistant infections and redefining the eradication of biofilms.
    Keywords:  Biofilm eradication; Commercialization; Micromotors; Nanomotors; Regulatory bottlenecks
    DOI:  https://doi.org/10.1016/j.biomaterials.2025.123715
  28. Adv Skin Wound Care. 2025 Sep 22.
    Use of Oral Antibiotics for Diabetic Foot Osteomyelitis: A Systematic Review.
    Siddhartha Sood, Ryan Geng, Jihad Waked, Asfandyar Mufti, Aswen Sriranganathan, Ronald Gary Sibbald.
      The optimal treatment modality for diabetic foot osteomyelitis (DFO) remains unclear. The current guidelines from Diabetes Canada recommend the use of oral antibiotics and/or intravenous antibiotics with no preferred agent or route of administration. This report aimed to evaluate the current evidence surrounding oral antibiotic therapy for DFO. Embase and MEDLINE databases were searched for original articles written in English that reported efficacy and safety data on oral antibiotic use for this indication. Twenty-six unique studies were included, encompassing 972 patients treated with oral antibiotics. The mean age was 64.6 years (range: 30 to 90 y). When used as monotherapy, the complete resolution and partial resolution rate for oral antibiotic therapy were 75.2% (539/717) and 3.2% (23/717), respectively. When used as a step-down therapy after intravenous antibiotics, the complete and partial resolution rate for oral antibiotics were 56.5% (155/255) and 20.4% (52/255), respectively. No resolution of DFO resulting in refractory infection or amputation was observed in 155 (21.6%) cases of oral antibiotics monotherapy and 59 (23.1%) of step-down therapy. Recurrence rates for oral antibiotics monotherapy and step-down therapy were 5.4% (39/717) and 3.9% (10/255), respectively. Oral antibiotic therapy demonstrates favorable outcomes in DFO comparable to intravenous treatment. Oral antibiotic therapy may be especially useful in low-resource settings where hospital beds are limited and in situations where patients require ambulation. Nonetheless, patients should be counselled on the vital importance of adherence, and resource stewardship should be practiced by health care providers to avoid antibiotic resistance.
    GENERAL PURPOSE: To present a systematic review article evaluating the utility of oral antibiotics for the treatment of diabetic foot osteomyelitis.
    TARGET AUDIENCE: This continuing education activity is intended for physicians; physician assistants; nurse practitioners; podiatrists/other foot specialists; and nurses with an interest in skin, wound, and diabetic foot care.
    LEARNING OBJECTIVES/OUTCOMES: After completing this continuing education activity, the participant should be better able to:Summarize the evidence the authors considered when evaluating the utility of oral antibiotics for diabetic foot osteomyelitis.Select the characteristics of the participants and settings in which oral antibiotic therapy was utilized.Identify the results of the authors' study assessing the use of oral antibiotics.Discuss potential situations in which oral antibiotic therapy may provide favorable outcomes as monotherapy or in conjunction with intravenous antibiotics for diabetic foot osteomyelitis.
    Keywords:  diabetic foot infection; diabetic foot osteomyelitis; evidence based; oral antibiotic; systematic review
    DOI:  https://doi.org/10.1097/ASW.0000000000000343
  29. Int J Mol Sci. 2025 Sep 20. pii: 9193. [Epub ahead of print]26(18):
    Catheter-Associated Urinary Tract Infections: Understanding the Interplay Between Bacterial Biofilm and Antimicrobial Resistance.
    Desiye Tesfaye Tegegne, Iain J Abbott, Błażej Poźniak.
      The increasing use of urinary catheters in healthcare, driven by an aging population and escalating antimicrobial resistance, presents both benefits and challenges. While they are essential to managing urinary retention and enabling precise urine output monitoring, their use significantly increases the risk of catheter-associated urinary tract infections (CAUTIs), the most common type of healthcare-associated infection. CAUTI risk is closely linked to the duration of catheterization and the formation of bacterial biofilms on catheter surfaces. These biofilms, often composed of polymicrobial communities encased in an extracellular matrix, promote persistent infections that are highly resistant to conventional antimicrobial therapies. Common CAUTI uropathogens include E. coli, E. faecalis, P. aeruginosa, P. mirabilis, K. pneumoniae, S. aureus, and Candida spp. The complexity and resilience of these biofilm-associated infections underscore the urgent need for innovative treatment strategies. Therefore, dynamic in vitro bladder infection models, which replicate physiological conditions such as urine flow and bladder voiding, have become valuable tools for studying microbial behavior, biofilm development, and therapeutic interventions under real clinical conditions. This review provides an overview of CAUTIs, explores the role of biofilms in sub-optimal responses to antimicrobial treatment and advances in model systems, and presents promising new approaches to combating these infections.
    Keywords:  CAUTIs; an in vitro dynamic model; antimicrobial resistance; bacterial biofilm; urinary catheter
    DOI:  https://doi.org/10.3390/ijms26189193
  30. Gut Pathog. 2025 Sep 26. 17(1): 72
    Global research landscape and advancements on the links between the gut microbiome and insulin resistance: hot issues, trends, future directions, and bibliometric analysis.
    Sa'ed H Zyoud, Muna Shakhshir, Amani S Abushanab, Amer Koni, Moyad Shahwan, Ammar A Jairoun, Banan M Aiesh, Samah W Al-Jabi.
       BACKGROUND: There is increasing evidence suggesting that the gut microbiota plays a key role in the development of insulin resistance (IR). Therefore, the present bibliometric study aimed to characterize the development trends and research hotspots of publications related to the gut microbiota and IR.
    METHODS: Publications on the gut microbiota and IR between 2015 and 2024 were retrieved from the Scopus database. Bibliometric analyses were conducted with the VOSviewer version 1.6.20 software program.
    RESULTS: The Scopus query (15 June 2025) retrieved 584 publications on the gut microbiota and IR. Most were research articles (n = 480, 82.19%), followed by reviews (n = 82, 14.04%). Output is highly skewed toward East Asia and North America, with China leading the list with 254 papers (43.49%), followed by the United States (96; 16.44%), Canada (44; 7.53%), and Germany (27; 4.62%). Term-cooccurrence mapping in VOSviewer (v1.6.20) of the 251 high-frequency keywords (≥ 15 occurrences) resolved three thematic clusters: Cluster 1 focused on the high-fat-diet gut-liver axis; Cluster 2 examined patient-centered epidemiology and clinical trials; and Cluster 3 investigated inflammatory and metabolic signalling.
    CONCLUSIONS: The annual number of publications on the gut microbiota and IR has increased rapidly in the past ten years, demonstrating that the gut microbiota and IR have the potential to be researched precisely and are attracting increasing attention. The findings of this study can help researchers explore new directions for future research in this area and could serve as a reference for future academic research.
    Keywords:  Bibliometric; Gut microbiota; Insulin resistance; Insulin sensitivity; Microbiome; Scopus; VOSviewer
    DOI:  https://doi.org/10.1186/s13099-025-00749-6
  31. MethodsX. 2025 Dec;15 103599
    Comparative analysis of phage cocktail activity against uropathogenic E. coli strains using spot overlay assay.
    Steven Arcidiacono, Robert Stote.
      Spot overlay assays are a common method for measuring phage activity against target microorganisms and determining % host range activity. Dilutions of phage demonstrate activity by creating a zone of clearing indicative of bacterial killing; however, this yields only semi-quantitative results for each target strain tested. In addition, zones can be completely clear or incomplete cloudy zones of varying intensity. These factors make it difficult to compare the overall strength of activity between monophages or phage cocktails when numerous bacterial strains are involved. Here we demonstrate a method to analyze spot overlay results to provide insight beyond just host range activity; three phage cocktails with host range activity of 92-96 % had different overall activities. While the spot overlay is a qualitative assay, consolidation of activity results can derive semi-quantitative information. This method converts activity of phage dilutions from a spot overlay assay into an overall activity of cocktails for comparison. Our method:•Uses standard laboratory protocol for analysis•Expands information beyond host range activity•Consolidates results of all strains tested to assess overall cocktail strength of activity for comparison.
    Keywords:  Cocktail activity; Comparative analysis; Host range; Phage cocktails; Spot overlay assay; Zones of clearing
    DOI:  https://doi.org/10.1016/j.mex.2025.103599
  32. Antibiotics (Basel). 2025 Aug 28. pii: 865. [Epub ahead of print]14(9):
    Biofilms Exposed: Innovative Imaging and Therapeutic Platforms for Persistent Infections.
    Manasi Haval, Chandrashekhar Unakal, Shridhar C Ghagane, Bijay Raj Pandit, Esther Daniel, Parbatee Siewdass, Kingsley Ekimeri, Vijayanandh Rajamanickam, Angel Justiz-Vaillant, Kathy-Ann A Lootawan, Fabio Muniz De Oliveira, Nivedita Bashetti, Tatheer Alam Naqvi, Arun Shettar, Pramod Bhasme.
      Biofilms constitute a significant challenge in the therapy of infectious diseases, offering remarkable resistance to both pharmacological treatments and immunological elimination. This resilience is orchestrated through the regulation of extracellular polymeric molecules, metabolic dormancy, and quorum sensing, enabling biofilms to persist in both clinical and industrial environments. The resulting resistance exacerbates chronic infections and contributes to mounting economic burdens. This review examines the molecular and structural complexities that drive biofilm persistence and critically outlines the limitations of conventional diagnostic and therapeutic approaches. We emphasize advanced technologies such as super-resolution microscopy, microfluidics, and AI-driven modeling that are reshaping our understanding of biofilm dynamics and heterogeneity. Further, we highlight recent progress in biofilm-targeted therapies, including CRISPR-Cas-modified bacteriophages, quorum-sensing antagonists, enzyme-functionalized nanocarriers, and intelligent drug-delivery systems responsive to biofilm-specific cues. We also explore the utility of in vivo and ex vivo models that replicate clinical biofilm complexity and promote translational applicability. Finally, we discuss emerging interventions grounded in synthetic biology, such as engineered probiotic gene circuits and self-regulating microbial consortia, which offer innovative alternatives to conventional antimicrobials. Collectively, these interdisciplinary strategies mark a paradigm shift from reactive antibiotic therapy to precision-guided biofilm management. By integrating cutting-edge technologies with systems biology principles, this review proposes a comprehensive framework for disrupting biofilm architecture and redefining infection treatment in the post-antibiotic era.
    Keywords:  antimicrobial resistant; bacteria; biofilm; biofilm quantification; nanomaterials; quorum sensing
    DOI:  https://doi.org/10.3390/antibiotics14090865
  33. Int J Mol Sci. 2025 Sep 17. pii: 9065. [Epub ahead of print]26(18):
    Probiotics in IBD: Evidence and Perspectives on Patient Health and Disease Management.
    Emília Hijová.
      Inflammatory bowel disease (IBD) includes two distinct diseases: ulcerative colitis (UC) and Crohn's disease, affecting people worldwide regardless of age and gender. It appears that a combination of many factors, primarily genetic background, environmental, host immune response, and a state of reduced microbial diversity are associated with IBD. Gut modulation by probiotics application represents one of the potential strategies for the prevention or treatment of IBD. The gut microbiota has the ability to influence host physiology either directly or through microbial metabolites. This review summarizes human randomized clinical trials that evaluate the usefulness of various probiotics in relation to the treatment, prevention, and maintenance of disease remission.
    Keywords:  Crohn’s disease; probiotics; ulcerative colitis
    DOI:  https://doi.org/10.3390/ijms26189065
  34. Chembiochem. 2025 Sep 26. e202500604
    Biocompatible Metal Sulfide-Based Nanomaterials for Antimicrobial and Wound Healing Applications.
    Ashmalina Rahman, Mohammad Mansoob Khan.
      The progress of innovative antimicrobial coatings and therapeutic approaches is becoming increasingly important for effective wound healing. Due to their unique properties, chalcogenides, particularly metal sulfides, have gained significance in antibacterial and wound healing applications. By promoting tissue regeneration and lowering scarring, these materials can improve wound healing and treat bacterial infections. This review summarizes recent advancements in metal sulfides for antimicrobial and wound healing applications, aiming to combat infections, diseases, and facilitate healing. The different antimicrobial mechanisms of metal sulfides are also highlighted. The prospects and limitations for eventual translation to a real-life application are also discussed. Thus, metal sulfide-based materials offer promising insight into the development of novel antimicrobial materials and wound dressings.
    Keywords:  antimicrobial agents; biocompatible; chalcogenides; metal sulfides; microbes; wound healing
    DOI:  https://doi.org/10.1002/cbic.202500604
  35. Virol J. 2025 Sep 26. 22(1): 304
    Bacteriophage T4 propagation in E.coli exposed to severe substrate limitation.
    Ana Lisac, Aleš Podgornik.
      Understanding bacteriophage propagation on bacteria in different physiological conditions is imperative for predicting phage therapy efficacy on various bacterial infections, especially chronic ones. We investigated phage T4 propagation on bacteria E.coli grown in a chemostat at very low dilution rates extending down to 0.027 h-1 and bacteria exposed to nutrient deprivation. An increase in adsorption constant and latent period with dilution rate D decrease and burst size being proportional to dilution rate (D) was confirmed, consistent with previously published results, extending validity of previous findings. Additional bacterial exposure to starvation, either through nutrient cessation or transferring bacteria into SM buffer, sustained phage propagation during first hours of starvation and diminished to formation of a single phage per infected cell after 24 h. Nutrient deprivation effects were investigated on fast growing bacteria and bacteria in a death phase. While no phage generation was observed within bacteria in death phase, fast growing bacteria transferred into SM buffer generated a single phage within 48 h without lysis, indicating that bacterial exposure to nutrient depleted conditions triggers a so called "scavenger response" whose intensity depends on starvation exposure time.
    Keywords:  Bacteriophage T4; Bacteriophage growth parameters; Chemostat; E. coli; Scavenger response; Substrate limitation
    DOI:  https://doi.org/10.1186/s12985-025-02934-0
  36. Gels. 2025 Sep 03. pii: 705. [Epub ahead of print]11(9):
    Biological Models for Evaluating Hydrogel-Based Formulations in Wound Healing.
    Ioana Baldea, Ioana Georgeta Grosu, Sahar Ghafury, Cristian Golat, Doriane Doubali, Ana-Maria Vestemean, Aris Nicolas Cedorge, Ilinca Florian, Michael Yiannoulatos, Muhammad Mudassir Wajahat, Lorenzo Raoul Silli, Thesseus Stavrou, Daniela Rodica Mitrea.
      Skin, the largest organ of the human body, serves as a critical physico-chemical barrier against environmental insults and plays essential roles in hydration, thermoregulation, immune defense, and metabolic functions. Wound healing is a complex, multistage biological process involving hemostasis, inflammation, proliferation, and remodeling. Hydrogels have emerged as a promising class of wound dressings due to their high moisture retention, biocompatibility, and ability to mimic the extracellular matrix, thereby supporting accelerated healing and controlled drug delivery. This review provides a comprehensive overview of current hydrogel types-classified by origin, crosslinking mechanisms, and responsiveness to stimuli-and evaluates their use in experimental research on in vitro, ex vivo, and in vivo wound healing models. Furthermore, clinical applications of hydrogels in wound therapy are discussed. Advances in semisynthetic and stimuli-responsive hydrogels, along with improved testing models, offer enhanced therapeutic potential and underscore the need for continued innovation to optimize wound care outcomes and alleviate healthcare burdens.
    Keywords:  burn wound model; crosslinked hydrogels; full-thickness skin model; hydrogel-based dressings; reconstructed human epithelium; scratch assay; surgical wound model; wound healing models
    DOI:  https://doi.org/10.3390/gels11090705
  37. Commun Med (Lond). 2025 Sep 24. 5(1): 394
    War impact on antimicrobial resistance and bacteriological profile of wound infections in Ukraine.
    Viktoriia M Holubnycha, Olena V Kholodylo.
       BACKGROUND: Infections and antimicrobial resistance are among the main public health issues in the countries affected by war. This study evaluates war's impact on wound microbiome and antimicrobial resistance distribution among patients treated in Ukrainian civilian hospitals.
    METHODS: The patients with combat wounds were treated in the civilian hospitals located in the Northeast of Ukraine from January to April 2024. The wound samples were examined. The isolated microorganisms were identified with further investigation of antimicrobial resistance profiles.
    RESULTS: Here we show the data obtained from the examination of seventy-three wounded soldiers. Wound infections are associated with severe trauma and the middle age of patients. Bacteria were isolated in 56.16% samples with a predominance of gram-negative bacilli. The most frequent isolates are A. baumannii (36%), E. faecalis (12%), and B. cereus (12%). The frequency of multidrug resistance is 84.6%. Each isolated species has a certain sensitivity profile to antibiotics. The number of multidrug-resistant strains among gram-negative bacteria is higher than among gram-positive ones.
    CONCLUSIONS: This study shows the dominance of gram-negative bacilli in military personnel with a higher frequency of multidrug-resistant isolates. These complicate the healing process and promote the spread of multidrug-resistant strains within healthcare settings.
    DOI:  https://doi.org/10.1038/s43856-025-01056-6
  38. Adv Mater. 2025 Sep 25. e08500
    Probiotic-Based Materials as Living Therapeutics.
    Laura Sabio, Graham J Day, Manuel Salmeron-Sanchez.
      The growing demand for safer, more targeted therapeutics requires the development of advanced biomaterials. Among these, Engineered Living Materials (ELMs)-which integrate synthetic biology with material science-are emerging as promising platforms for biomedical applications. This review focuses on a subclass of ELMs based on genetically engineered probiotics combined with matrices, that are termed Probiotic Living Materials (PLMs) to differentiate them from Living Biotherapeutic Products (LBPs). Recent studies highlight PLM's potential in addressing different health conditions, offering targeted and dynamic therapies. However, PLMs face multiple challenges to be implemented in clinics, including a lack of robust genetic toolkits for probiotic engineering, concerns about biosafety (e.g., horizontal gene transfer or non-desirable biological activity), difficulties in translating preclinical results to humans, and the absence of clear regulatory guidance for clinical use. This review first explores the fundamental features of ELMs, then provides an overview of probiotics, followed by recent advances in the design of engineered PLMs for biomedical applications, particularly in biosensing development, infection treatment, bone repair, wound healing, vaginal imbalances, gut-related conditions, and cancer therapy. Finally, biosafety issues and current gaps in regulatory frameworks to ensure safe and effective use of PLMs, with a particular focus on vulnerable populations, are discussed.
    Keywords:  engineered living materials; probiotics; therapeutics
    DOI:  https://doi.org/10.1002/adma.202508500
  39. Eur Respir Rev. 2025 Jul;pii: 240284. [Epub ahead of print]34(177):
    The respiratory tract virome: unravelling the role of viral dark matter in respiratory health and disease.
    Martha Purcell, Jodie Ackland, Karl J Staples, Anna Freeman, Tom M A Wilkinson.
      The human respiratory tract virome is an underexplored component of the microbiome that includes eukaryotic viruses, bacteriophages and archaeal viruses. The respiratory virome represents a dynamic and heterogeneous ecosystem, shaped by host, environmental and microbial factors. Advances in metagenomic sequencing have expanded our understanding of virome composition, dynamics and potential roles in health and disease. Despite increasing interest, virome research remains fragmented and often secondary to bacteriome studies. Challenges in study design, genomic characterisation and interpretation limit consistent conclusions. This review summarises current knowledge of the respiratory virome in health and across acute and chronic respiratory diseases, including acute respiratory infection, asthma, COPD, cystic fibrosis and bronchiectasis. While each condition is distinct, they share features of airway inflammation and immune dysregulation where the virome may act as a modifier or marker. Across these syndromes, emerging evidence highlights the consistent detection of respiratory viruses including potential commensals, such as Anelloviridae, and the often-overlooked role of bacteriophages. We also discuss the concept of viral dark matter, where large proportions of sequence data remain unclassified, potentially representing novel viral taxa. Technical and conceptual challenges are evaluated, alongside recent methodological innovations such as meta-transcriptomics and viral enrichment protocols. We outline how standardised, multi-omic and longitudinal approaches are urgently needed to clarify the virome's functional role, interactions with immunity and microbial communities and its utility as a biomarker or therapeutic target.
    DOI:  https://doi.org/10.1183/16000617.0284-2024
  40. Int J Infect Dis. 2025 Sep 18. pii: S1201-9712(25)00297-8. [Epub ahead of print] 108075
    Personalized aerosolised bacteriophage treatment of a pulmonary infection due to carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae in an infant.
    Huiyuan Yan, Nannan Wu, Jinlan Zhou, Anjie Jin, Mengjun Cheng, Jianfang Liu, Qian Yang, Chuanqing Wang, Leiyan He, Weiming Chen, Yixue Wang, Zhenyu Zhang, Caiyan Zhang, Weili Yang, Guoping Lu, Gangfeng Yan.
      A 9-month-old ICU patient with persistent carbapenem-resistant Acinetobacter baumannii pneumonia developed a secondary infection of carbapenem-resistant Klebsiella pneumoniae. A customized, pre-optimized phage cocktail was administered twice daily for 3 consecutive days, resulting in eradication of the pathogens and reduction in their abundance in the lung and gut microbiota.
    Keywords:  carbapenem-resistant Acinetobacter baumannii; carbapenem-resistant Klebsiella pneumoniae; gut microbiota; infant; personalized phage therapy
    DOI:  https://doi.org/10.1016/j.ijid.2025.108075
  41. Adv Skin Wound Care. 2025 Oct 01. 38(9): 457-461
    Artificial Intelligence in Skin and Wound Care: Enhancing Diagnosis and Treatment With Large Language Models.
    Scott Nelson, Briana Lay, Alton R Johnson.
       ABSTRACT: Artificial intelligence (AI) is revolutionizing the landscape of skin and wound care by improving diagnostic accuracy, treatment effectiveness, and patient outcomes. Artificial intelligence-driven tools, including machine learning models and large language models (LLMs), enhance the precision of wound assessments, facilitate early infection detection, and streamline clinical workflows. In addition, these tools may aid in patient symptom reporting, bridging the communication gap between patients and health care providers. Current AI applications include image recognition for wound classification, patient-facing symptom-checking chatbots, and personalized treatment recommendations. The integration of AI technologies not only supports better clinical decision-making but also empowers patients through improved access, engagement, and education. These tools are currently aimed at supporting clinical decision-making, not replacing clinicians. Moving forward, the expansion of AI capabilities in skin and wound care holds great promise, driving cost-effective, scalable, and equitable health care solutions.
    Keywords:  artificial intelligence (AI); chronic wound; digital health; health care technology; large language models (LLMs); limb salvage; wound care
    DOI:  https://doi.org/10.1097/ASW.0000000000000353
  42. Drug Dev Ind Pharm. 2025 Sep 22. 1-21
    Advances in Novel Drug Delivery Systems: A Focus on Nanoparticles and Mucoadhesive Technologies.
    Ravi Sangavi, Sulekha Khute, Paranthaman Subash.
       OBJECTIVE: To explore the advancements and therapeutic potential of nanocarrier-based drug delivery systems in improving drug administration, targeting efficiency, and patient outcomes, particularly in complex disease management.
    SIGNIFICANCE: Traditional drug delivery methods often suffer from limited targeting ability, poor bioavailability, and increased side effects. Nanocarriers, such as liposomes, dendrimers, polymeric nanoparticles, and solid lipid nanoparticles, offer innovative solutions by enabling site-specific delivery, controlled release, and enhanced therapeutic indices, thereby transforming pharmaceutical care.
    METHODS: This review examines the current literature and recent innovations in nanocarrier design and application. It highlights stimulus-responsive systems (e.g., pH- or temperature-sensitive nanocarriers) and assesses their roles in treating conditions such as cancer, rheumatoid arthritis, and neurological disorders. This study also analyzes technological trends and translational challenges in clinical applications, including regulatory and safety concerns.
    RESULTS: Recent developments in nanotechnology have enabled the creation of multifunctional, targeted, and stimuli-responsive nanocarriers capable of delivering therapeutic agents with improved precision and efficacy. These systems significantly enhance drug absorption and retention at the target site, provide sustained release, and minimize systemic side effects of the drug. Preclinical and early clinical data support their effectiveness in overcoming the limitations of conventional therapies.
    CONCLUSIONS: Nanocarrier-based drug delivery systems represent a paradigm shift in therapeutic strategies, offering precision-targeted treatment with improved efficacy and safety. Despite regulatory and translational challenges, continued research and innovation are accelerating their path to clinical adoption, establishing nanocarriers as the cornerstone of personalized medicine in cancer therapy.
    Keywords:  Controlled release; Drug delivery systems; Nanocarriers; Polymeric nanoparticles; Targeted therapy
    DOI:  https://doi.org/10.1080/03639045.2025.2564364
  43. Antimicrob Agents Chemother. 2025 Sep 26. e0047525
    Characterization of new mouse models of acute and chronic Mycobacterium abscessus infection for antimicrobial drug screening.
    Ilham M Alshiraihi, Ha Lam, Brennen T Troyer, Kristina N Tran, Malik Zohaib Ali, Daryl K Conner, Abigail Godelfer, Camron Pearce, Mary Jackson, Marcela Henao-Tamayo, Sara E Maloney Norcross, Bernd Meibohm, Richard E Lee, Mercedes Gonzalez-Juarrero, Andres Obregon-Henao.
      Mycobacterium abscessus (MAB), a rapidly growing non-tuberculous mycobacterium, is becoming increasingly recognized as a significant pathogen affecting humans. These bacteria particularly impact individuals with cystic fibrosis (CF), non-CF bronchiectasis, and compromised immune systems. Treating pulmonary infections with MAB is challenging due to the bacteria's inherent and acquired resistance to many antibiotics, including most anti-tuberculosis antibiotics. Antibiotic therapy of MAB infection is lengthy, involves multiple oral and parenteral administered drugs, induces significant toxicity, and, on many occasions, fails to cure. Consequently, developing more effective antibiotics has become a high priority. Preclinical studies to evaluate antibiotic efficacy against MAB are challenging because they fail to establish a progressive and sustained pulmonary infection in commonly used animal models. To address this issue, the course of MAB pulmonary infection was evaluated in 15 immunocompetent or deficient mouse strains. We report bacterial burden and histopathology and classify the models according to their ability to clear or sustain progressive infection beyond 28 days. We also examined the potential of these models for drug screening. Our findings provide a foundation for selecting suitable mouse models of pulmonary MAB infection for drug discovery.
    Keywords:  Mycobacterium; abscessus; drug testing; models; mouse; preclinical
    DOI:  https://doi.org/10.1128/aac.00475-25
  44. China CDC Wkly. 2025 Sep 12. 7(37): 1175-1181
    Confronting the Antimicrobial Resistance Crisis in China: Emerging Superbugs, Genomic Surveillance, and Innovative Countermeasures.
    Qian Tong, Liping Zeng, Yixin Ge, Jia Jia.
      The antimicrobial resistance (AMR) crisis in China has escalated into a critical public health threat. Extensive antibiotic use in both clinical and agricultural settings has created strong selective pressures, promoting the emergence of resistant strains and accelerating their dissemination. This increasing threat is exemplified by the rapid spread of multidrug-resistant bacteria. Consequently, genomic surveillance of these pathogens and the development of effective countermeasures are urgently needed. In this paper, we highlight three critical dimensions of the AMR challenge in China, which include the recent emergence of resistant bacteria, genomic surveillance efforts, and progress in the development of novel antimicrobial agents. By synthesizing recent research on the evolutionary dynamics of drug-resistant pathogens in China and outlining innovative antimicrobial strategies, this study provides insights to guide evidence-based antimicrobial stewardship programs.
    Keywords:  Antimicrobial Resistance; Drug-resistant Bacteria; Novel Antimicrobial Agents
    DOI:  https://doi.org/10.46234/ccdcw2025.197
  45. Bioinformatics. 2025 Sep 24. pii: btaf531. [Epub ahead of print]
    SPAED: Harnessing AlphaFold Output for Accurate Segmentation of Phage Endolysin Domains.
    Alexandre Boulay, Emma Cremelie, Clovis Galiez, Yves Briers, Elsa Rousseau, Roberto Vázquez.
       SUMMARY: SPAED is an accessible tool for the accurate segmentation of protein domains that leverages information contained in the predicted aligned error (PAE) matrix obtained from AlphaFold to better identify domain-linker boundaries and detect terminal disordered regions. On a dataset of 376 bacteriophage endolysins (proteins that degrade the bacterial cell wall), SPAED achieves a mean intersect-over-union score of 96% and a domain-boundary-distance score of 89% compared to 94% and 70%, respectively, for the state-of-the-art tool Chainsaw.
    AVAILABILITY AND IMPLEMENTATION: Implemented in Python, SPAED is accessible on the web (https://spaed.ca) and available for download from https://github.com/Rousseau-Team/spaed or https://pypi.org/project/spaed. The data used to test SPAED can be found at https://doi.org/10.5281/zenodo.15285860.
    SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
    DOI:  https://doi.org/10.1093/bioinformatics/btaf531
  46. J Wound Ostomy Continence Nurs. 2025 Sep-Oct 01;52(5):52(5): 417-420
    Medical Malpractice in Wound Care: A Multiple Case Series.
    Lydia Corum.
       BACKGROUND: Issues related to wound assessment, treatment, and wound etiology are frequently scrutinized in medical malpractice cases. As patients and their families become increasingly knowledgeable about wound care, specialists must adopt evidence-based practices and engage patients in care planning to reduce litigation risks. Practical communication skills are critical when interacting with patients with wounds, and meticulous documentation of these interactions can assist clinical staff to avoid potential medical malpractice claims. This article focuses on identifying the essential components of a medical malpractice case and provides an analysis of 3 illustrative cases. By examining these cases, health care professionals can gain valuable insights into the complexities of medical malpractice and develop strategies to enhance patient care and minimize legal risks.
    CASES: In Case 1, the court affirmed the authority of wound care nurses in Arizona to provide expert testimony regarding causation in pressure injury cases. In the second case, a wrongful death claim resulting from sepsis secondary to a urinary tract infection and malnutrition is presented that underscores fundamental issues related to the mismanagement of a deep tissue pressure injury. Finally, case 3 describes a patient with renal failure managed by dialysis whose foot wound progressed to gangrene due to inadequate reporting practices, emphasizing the necessity of effective communication among health care providers.
    CONCLUSION: Ongoing and effective education is vital for health care professionals to enhance wound care practices. Engaging in webinars, conferences, and reading professional literature is essential for maintaining expertise and ensuring effective testimony. Education and experience are critical not only for clinical practice but also for navigating legal challenges.
    Keywords:  Pressure injury medical malpractice cases; Wound care documentation; Wound care medical malpractice cases; Wound care nurse as a legal nurse consultant; Wound care standards of care
    DOI:  https://doi.org/10.1097/WON.0000000000001214
  47. Microorganisms. 2025 Sep 19. pii: 2194. [Epub ahead of print]13(9):
    An Overview of the Epidemiology of Multidrug Resistance and Bacterial Resistance Mechanisms: What Solutions Are Available? A Comprehensive Review.
    Victoria Birlutiu, Rares-Mircea Birlutiu.
      Antimicrobial resistance has emerged as one of the most critical public health challenges of the 21st century, threatening to undermine the foundations of modern medicine. In 2019, bacterial infections accounted for 13.6% of all global deaths, with more than 7.7 million fatalities directly attributable to 33 bacterial pathogens, most prominently Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Resistance mechanisms are multifactorial, encompassing enzymatic degradation, target modification, efflux pump overexpression, reduced membrane permeability, and biofilm formation, often in combination, leading to multidrug-resistant, extensively drug-resistant, and pandrug-resistant phenotypes. Alarmingly, projections estimate that by 2050 AMR could result in over 10 million deaths annually. This comprehensive review synthesizes global epidemiological data, insights into bacterial resistance mechanisms, and emerging therapeutic solutions, including novel antibiotics such as lasso peptides and macrocyclic peptides (e.g., zosurabalpin), naturally derived compounds (e.g., corallopyronin, clovibactin, chlorotonil A), and targeted inhibitors (e.g., Debio 1453 for Neisseria gonorrhoeae). Addressing the AMR crisis requires coordinated international efforts, accelerated drug discovery, and the integration of innovative non-antibiotic approaches to preserve the efficacy of existing therapies and ensure preparedness against future bacterial threats.
    Keywords:  antimicrobial resistance; bacterial resistance mechanisms; extensively drug-resistant pathogens; global epidemiology; multidrug-resistant bacteria; novel antibiotics; pandrug resistance
    DOI:  https://doi.org/10.3390/microorganisms13092194
  48. Vet Sci. 2025 Aug 26. pii: 817. [Epub ahead of print]12(9):
    Isolation of Lytic Bacteriophages of Escherichia coli and Their Combined Use with Antibiotics Against the Causative Agents of Colibacillosis in Calves.
    Pavel G Alexyuk, Andrey P Bogoyavlenskiy, Kuralay S Akanova, Yergali S Moldakhanov, Timur T Kerimov, Nadezhda S Sokolova, Vladimir E Berezin, Madina S Alexyuk.
      The spread of antibiotic-resistant pathogenic Escherichia coli poses a serious threat to calf health on livestock farms. With the decline in antibiotic therapy effectiveness, alternative approaches such as phage therapy are urgently needed. This study aimed to isolate lytic E. coli bacteriophages, characterize their properties, and evaluate the synergistic effects of their combined use with veterinary antibiotics against colibacillosis pathogens in calves. As a result of the work, 4 bacteriophages were isolated from wastewater from various cities of Kazakhstan: vB_EcoS_ABO/4, vB_EcoM_PL/4, vB_Eco_CWW/26, vB_EcoM_ShWW/46. Morphological, biological, and genomic analyses showed that the phages belong to different genera of the Caudoviricetes class, possess high lytic activity, broad host range, environmental stability, and lack genes associated with lysogeny, antibiotic resistance, or virulence. Interaction studies with antibiotics revealed synergistic or additive effects in over 75% of cases. These findings highlight the strong potential of the isolated bacteriophages for independent or adjunctive use in the treatment and prevention of colibacillosis in calves. However, further in vivo studies are required to definitively confirm their therapeutic efficacy.
    Keywords:  Escherichia coli; antibiotic resistance; bacteriophage; colibacillosis; phage therapy; synergy; whole-genome sequencing
    DOI:  https://doi.org/10.3390/vetsci12090817
  49. Medicina (Kaunas). 2025 Sep 05. pii: 1605. [Epub ahead of print]61(9):
    Airway Microbiome in Children with Cystic Fibrosis: A Review of Microbial Shifts and Therapeutic Impacts.
    Georgiana Buruiană, Cristina Mihaela Sima, Dana-Teodora Anton-Păduraru, Aida Corina Bădescu, Cătălina Luncă, Alexandru Duhaniuc, Olivia Simona Dorneanu.
      Even with significant advances in therapeutic interventions and monitoring protocols, cystic fibrosis (CF) remains a critical pediatric health challenge affecting respiratory function and long-term patient outcomes. CF, caused by mutations in the CFTR gene, disrupts normal mucociliary clearance and creates conditions for chronic respiratory infections. The disorder affects individuals globally, with pediatric patients facing particularly complex microbial challenges that evolve throughout childhood growth. CF poses significant risks with progressive lung function decline and increased mortality, leading to potential short- and long-term respiratory complications. There is a growing concern among clinicians about the dynamic nature of airway microbial communities, with classical pathogens like Pseudomonas aeruginosa and Staphylococcus aureus showing sequential emergence patterns that complicate treatment strategies, highlighting an urgent need for microbiome-informed therapeutic approaches. Our review aims to provide a comprehensive overview of airway microbiome evolution in pediatric CF patients. We outline the molecular and ecological mechanisms involved in microbial community progression, as well as the age-related trajectories leading to pathogen-dominated ecosystems and the subsequent complications associated with microbial dysbiosis. Given the widespread implications of disrupted microbial balance on disease progression, our review also presents the temporal landscape of airway microbiome changes, including age-related microbial succession patterns, and explores the underlying mechanisms driving these ecological shifts. The progressive nature of microbial simplification frequently leads to treatment challenges, emphasizing the importance of investigating microbiome-targeted therapeutic interventions. Therefore, in this review, we also explore established therapeutic strategies, including CFTR modulators and probiotics, which could offer promising approaches to maintaining microbial balance and improving outcomes in pediatric CF patients.
    Keywords:  CFTR modulators; airway pathogens; antibiotics; cystic fibrosis; lung microbiome; microbial succession; pediatric; probiotics
    DOI:  https://doi.org/10.3390/medicina61091605
  50. Children (Basel). 2025 Sep 17. pii: 1248. [Epub ahead of print]12(9):
    A Comprehensive Review of Pediatric Necrotizing Pneumonia.
    Manette Ness-Cochinwala, Balagangadhar R Totapally.
      Necrotizing pneumonia is a serious complication of pediatric pneumonia, characterized by liquefaction and cavitation of the lung parenchyma. Streptococcus pneumoniae and Staphylococcus aureus are the most implicated organisms. Mycoplasma pneumoniae has been an increasingly recognized pathogen, especially is Asian and Pseudomonas aeruginosa is mainly noted in a higher percentage of patients with complex chronic conditions. Clinical presentation typically includes fever, respiratory distress, and failure to respond to standard antibiotic therapy. These patients are more likely to have pleural involvement in the form of effusion or empyema and a higher need for respiratory support. Diagnosis is typically through a combination of chest radiographs, lung ultrasound, and chest computed tomography. Management is primarily via prolonged intravenous antibiotics that cover the above organisms, though pleural drainage with fibrinolytics is often required. Surgical intervention is often reserved for refractory cases that fail initial fibrinolytic therapy. Prognosis is usually favorable in the short and long term, though early recognition and appropriate management are imperative to reduce the duration of illness and morbidity.
    Keywords:  complicated pneumonia; empyema; lung necrosis; pneumonia
    DOI:  https://doi.org/10.3390/children12091248
This page is being maintained by Thomas Krichel. It was last updated on 2025‒09‒28 at 9:20.