bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2025–11–16
forty papers selected by
Luca Bolliger, lxBio
  1. Regulation of phage therapy medicinal products: developments, challenges, and opportunities.
  2. Isolation and characterization of biofilm-disrupting proteus phage Premi.
  3. Efficacy of Phage Cocktails Against Biofilms Formed by Antibiotic-Resistant Bacteria.
  4. Bacteriophage endolysins.
  5. Phage-conjugated chlorin e6: A strategy overcoming phage resistance in biofilm eradication and wound infection therapy of carbapenem-resistant Acinetobacter baumannii.
  6. Biofilms and Chronic Wounds: Pathogenesis and Treatment Options.
  7. Interpretation guidance for MHRA regulatory considerations for phage therapeutic products.
  8. Resistance to last-resort antibiotics in enterococci.
  9. Identification and characterization of a novel plaque-invisible lytic single-stranded RNA phage.
  10. ProkBERT PhaStyle: accurate phage lifestyle prediction with pretrained genomic language models.
  11. Use of autologous whole blood clot for hard-to-heal diabetic foot ulcers: a case series.
  12. A comparative analysis of sharp debridement devices for biofilm management in hard-to-heal wounds: a clinical assessment.
  13. The hitchhiker's guide to cross-species DNA delivery.
  14. Bacterial restriction-modification systems: mechanisms of defense against phage infection.
  15. Comparative genomics reveals diversity and taxonomic relationships among Clostridioides difficile phages.
  16. Dextran based hydrogel wound dressing with cytocompatible, anti-protein and antibacterial properties for infected wound healing.
  17. Unresolved challenges in wound healing: When science meets clinical need.
  18. Evaluating the Impact of Clear Dental Aligners on Dental and Periodontal Conditions, Oral Microbial Patterns, and the Immune System.
  19. Deciphering shared receptor usage in genomically unrelated bacteriophages infecting hypervirulent Klebsiella pneumoniae K1 ST23.
  20. Magnesium-Loaded Collagen/Hyaluronic Acid-Catechol Hydrogel Cross-Linked by Visible Light for Infected Wound Healing.
  21. From passive to active: Next-generation mechanically active dressings for wound healing.
  22. The Oral Microbiome, Oral Hyperpermeability, and Periodontitis in Metabolic Syndrome.
  23. Cryo-EM structure of bacteriophage Bas63 reveals structural conservation and diversity in the Felixounavirus genus.
  24. Wound Assessment and Management: Key Concepts in Laceration Repair.
  25. Application of a full-thickness placental allograft in complex wound management: a case series across diverse aetiologies.
  26. A synthetic gut microbiota provides an understanding of the maintenance and functional impact of phage.
  27. The Oral-Gut-Systemic Axis: Emerging Insights into Periodontitis, Microbiota Dysbiosis, and Systemic Disease Interplay.
  28. The Role Played by Imidazole Propionic Acid in Modulating Gut-Heart Axis and the Development of Atherosclerosis: An Explorative Review.
  29. Emerging landscape of bioinformatics and artificial intelligence applications in cell-penetrating peptide-based delivery.
  30. Factors affecting the effectiveness and safety of colistin in treating drug-resistant gram-negative bacterial infections: a meta-analysis.
  31. Design and application of synthetic human gut microbial communities.
  32. Sonic Serenity: Piezoelectric Nanomaterials Reshaping Wound Healing Paradigms.
  33. Introducing biofeedback-integrated laser therapy: a novel approach for enhancing scar treatment.
  34. Use of Negative Pressure Wound Therapy in Selected Cases to Facilitate Abdominal Wound Healing: A Multiple Case Series.
  35. A Review of Recent Advances in Fecal Microbiota Transplantation for the Treatment of Hepatic Encephalopathy.
  36. Novel Wound Care Practices in Bullous Pemphigoid: A Systematic Review.
  37. Hyperbaric Oxygenation Therapy as Adjunctive Treatment of Complex Wound Associated with Sterno-clavicular Septic Arthritis.
  38. Compliance with Clinical Guidelines and AI-Based Clinical Decision Support Systems: Implications for Ethics and Trust.
  39. Advances in hydrogels combined with photothermal/photodynamic therapy for bacterial infection.
  40. Progress and prospects of gut microbiota-targeted therapy for primary biliary cholangitis.
  1. Front Cell Infect Microbiol. 2025 ;15 1631359
    Regulation of phage therapy medicinal products: developments, challenges, and opportunities.
    Miriam Fuerst-Wilmes, Vanessa Respondek, Michael Schramm, Nils Lilienthal, Katrin Buss, Anja Duechting.
      Due to their biological properties, bacteriophages represent a regulatory specialty and, at the same time, a challenge with regard to medicinal product approval. Established European guidelines on pharmaceutical quality, preclinical development, and clinical development are only partially applicable. The growing threat posed by infections with multidrug-resistant bacteria has not only boosted the development of bacteriophages for the treatment of bacterial infections in recent years but has also led to substantial progress in adapting regulatory requirements. In 2024, harmonized quality criteria for phage therapy medicinal products and active substances were implemented for the first time in the European Pharmacopoeia. Future European pharmaceutical legislation and recent national acts such as the German Medical Research Act are intended to enable exemptions that address the specific characteristics of phage therapeutics and open new regulatory pathways. Increasing amounts of data on clinical use of phage therapeutics are being published; however, the anticipated breakthrough in the form of a demonstration of efficacy in randomized controlled clinical trials has not yet been achieved. Growing experience with innovative phage preparations has been utilized to adjust regulatory requirements. On the path to approval of a defined phage therapy medicinal product, the evidence-based demonstration of efficacy and safety in randomized controlled clinical trials is the next and decisive step.
    Keywords:  antibacterial treatment; antimicrobial resistance; bacteriophages; non-traditional product; phage therapy medicinal products; regulatory advice
    DOI:  https://doi.org/10.3389/fcimb.2025.1631359
  2. Sci Rep. 2025 Nov 13. 15(1): 39780
    Isolation and characterization of biofilm-disrupting proteus phage Premi.
    Guadalupe Valencia-Toxqui, Shobana Sugumar, Jolene Ramsey.
      Proteus mirabilis is a biofilm-forming, multidrug-resistant bacterium and one of the most common causes of catheter-associated urinary tract infections (CAUTIs). Phage therapy is an alternative method that can be used to address the problem of multidrug-resistance. In this study, we report isolation and characterization of virulent phage Premi. The phage exhibits lytic activity against 4 out of 30 clinical isolates of P. mirabilis tested and is stable when exposed to pH values between 3 and 11. Phage Premi demonstrated significant anti-biofilm activity against P. mirabilis, reducing 24-hour established biofilms by 59-68%. In the 42-kb Premi genome, functions were assigned for the 50 predicted protein-coding genes including those involved in DNA replication, DNA modification, and lysis. Structural proteins were verified using mass spectrometry of purified virions. A comparison of its genomic features and phylogenetic analysis revealed that phage Premi is a podophage member of the order Caudoviricetes sharing 96% nucleotide similarity with Proteus phage PM 85 and has a T7-like phage genomic organization. Our study shows that Premi effectively inhibits P. mirabilis biofilms and could be a promising antimicrobial agent for treating drug-resistant P. mirabilis infection.
    Keywords:  CAUTI; Multidrug-resistance; Phage; Podophage; Proteus; UTI
    DOI:  https://doi.org/10.1038/s41598-025-23545-3
  3. Infect Drug Resist. 2025 ;18 5789-5799
    Efficacy of Phage Cocktails Against Biofilms Formed by Antibiotic-Resistant Bacteria.
    Vadym Poniatovskyi, Volodymyr Shyrobokov, Arkadii Vodianyk, Alla Kharina, Oleksiy Shevchenko.
       Aim: The rapid spread of multidrug-resistant strains of Klebsiella pneumoniae and Pseudomonas aeruginosa, along with their ability to form biofilms on various medical devices, significantly complicate the treatment of infections caused by these microorganisms and render antibiotic therapy ineffective. In contrast, the use of bacteriophages is a promising alternative for combating antibiotic-resistant biofilm-forming strains of K.pneumoniae and P.aeruginosa.
    Methods: Two cocktails of 14 bacteriophages (nine Klebsiella phages and five Pseudomonas phages) were used to control biofilms formed by XDR (Extensively Drug-Resistant) strains of K. pneumoniae and P. aeruginosa under in vitro conditions. The K. pneumoniae strain harbored genes associated with biofilm formation fimH, mrkA, matBecp and antibiotic resistance blaNDM-1, blaKPC, blaOXA-48, blaCTX-M-1, blaTEM . The P. aeruginosa strain carried genes associated with biofilm formation algD, PslD, PelF and antibiotic resistance blaNDM-1 .Bacteriophages were isolated from the wastewater samples. Biofilms were formed on various substrates (glass slides, wells of polystyrene plates, and polyvinyl chloride vascular catheters) and analyzed using optical and scanning electron microscopy, as well as gentian violet staining assays.
    Results: The results demonstrated that bacteriophage cocktails could effectively degrade biofilms of K. pneumoniae and P. aeruginosa. Biofilms formed on catheter segments, polystyrene plate wells, and glass slides were treated with lytic bacteriophages at concentrations of at least 10^7 PFU/mL. After 24 h of treatment with phage cocktails, a 34.5% reduction in biofilm biomass was observed on the catheters for K. pneumoniae strain No. 361 and 34.1% for P. aeruginosa strain No. 7. In polystyrene plate wells, the reductions were 39.3% and 52.8%, respectively.
    Conclusion: The experimental results indicate the effectiveness of phage cocktails in reducing biofilm biomass and bacterial viability. Given the ability of phages to degrade biofilms, phage therapy may become a promising adjunct to standard treatment methods for infections caused by multidrug-resistant pathogens.
    Keywords:  Klebsiella pneumoniae; Pseudomonas aeruginosa; antimicrobial resistance; bacteriophages; biofilms
    DOI:  https://doi.org/10.2147/IDR.S547655
  4. Enzymes. 2025 ;pii: S1874-6047(25)00015-0. [Epub ahead of print]58 279-317
    Bacteriophage endolysins.
    Nidhi Prajapati, Dharmendra Prajapati, Anil Patani, Sherzodbek Tashbaev, Gulomov Gafurjon Shavkatbek Ugli, Ashish Patel.
      In the last phase of their life cycle, bacteriophages form lytic enzymes known as bacteriophage endolysins that destroy the bacterial cell wall and liberate new virions. Endolysins have emerged as high-scope antimicrobial agents, especially against Gram-positive infections, due to their specificity, rapid action, and ability to target essential cell wall components. Because bacterial resistance to endolysins continues to be rare, their unique mode of action places them at a strategic advantage over traditional antibiotics. They can now be employed to design synthetic or chimeric endolysins with enhanced activity and broadened host range, even against Gram-negative bacteria, due to advancements made in molecular biology and protein engineering. This chapter gives a thorough analysis of the structure of bacteriophage endolysins, mode of action, classification, therapeutic applications, and challenges. Their potential in clinical medicine, agriculture, food safety, and biotechnology are also discussed, focusing on how they can serve as a viable solution to the global antibiotic resistance issue.
    Keywords:  Antimicrobial resistance (AMR); Bacteriophage; Endolysin; Enzybiotics; Phage therapy
    DOI:  https://doi.org/10.1016/bs.enz.2025.06.008
  5. J Photochem Photobiol B. 2025 Nov 07. pii: S1011-1344(25)00205-2. [Epub ahead of print]273 113302
    Phage-conjugated chlorin e6: A strategy overcoming phage resistance in biofilm eradication and wound infection therapy of carbapenem-resistant Acinetobacter baumannii.
    Jianhui Su, Siyi Chen, Zhishen Huang, Haoxuan He, Huanhuan Zou, Xiaoyi Huang, Yongzhao Xie, Hongxia Zhao, Zhenbo Xu, Tao Lei, Juan Li, Haiyan Zeng.
      Carbapenem-Resistant Acinetobacter baumannii (CRAB) frequently causes biofilm-related infections that can exhibit extreme resistance to antibiotic therapy. Phage therapy shows promise as an alternative treatment, yet bacteria may develop resistance to it with prolonged use. Phage-photosensitizer combination therapy represents a novel antimicrobial strategy. This study aims to evaluate the efficacy of chlorin e6-functionalized phage in eradicating biofilms and treating CRAB infections, and to assess its sustained after effect following the emergence of phage resistance. The A. baumannii phage (ABP)-chlorin e6 conjugate (ABP-Ce6) was successfully synthesized and characterized. It preserved the phage's absorptive capacity and lytic activity while enhanced reactive oxygen species (ROS) production. Moreover, ABP-Ce6 demonstrated remarkable antibacterial activity comparable to ABP while exceeding that of Ce6, and showed superior performance in both inhibiting biofilm formation and disrupting existing biofilms in CRAB Ab1513. Significantly, although ABP exhibited no efficacy against the phage-resistant CRAB Ab1513-BIM12 due to its inability to achieve irreversible adsorption, the ABP-Ce6 maintained potent antibacterial and biofilm ablation effects against this strain, outperforming free Ce6. This sustained efficacy arises from ABP's reversible adsorption, which still enables proximity-driven Ce6 delivery to the target bacteria. In vivo, the ABP-Ce6 significantly enhanced mice wound healing for infections caused by CRAB Ab1513 and Ab1513-BIM12. In conclusion, ABP-Ce6 exhibits significant efficacy as a therapeutic agent against CRAB infections even after the bacteria develop resistance to phage therapy. This novel strategy may serve as a hopeful complementary strategy to phage therapy, thereby reducing delays in screening for new therapeutic phages.
    Keywords:  Antibacterial; Biofilm; Carbapenem-resistant Acinetobacter baumannii; Chlorin e6; Phage therapy; Phage-photosensitizer combination therapy; Wound infection
    DOI:  https://doi.org/10.1016/j.jphotobiol.2025.113302
  6. J Clin Med. 2025 Nov 02. pii: 7784. [Epub ahead of print]14(21):
    Biofilms and Chronic Wounds: Pathogenesis and Treatment Options.
    Annabel Z Shen, Mohamad Taha, Mahmoud Ghannoum, Stephen K Tyring.
      Introduction: Chronic wounds are a growing healthcare challenge, with infections being major complications that delay healing. Biofilms are structured microbial communities encased in extracellular polymeric substances. Biofilms confer antimicrobial resistance, promote inflammation, and protect pathogens from host defenses. These mechanisms make eradication difficult with standard therapies. Methods: A focused literature review was conducted using PubMed (2010-2025) to examine the role of biofilms in chronic wounds, diabetic foot ulcers (DFUs), and burn injuries, as well as conventional and emerging treatment strategies. Studies are included if they addressed microbial composition, host-microbe interactions, or therapeutic outcomes in clinical or translational models. Discussion: Biofilms are implicated in up to 60% of chronic wounds and more than half of burn wounds. In DFUs, both bacterial and fungal biofilms contribute to chronicity and impaired healing. Conventional treatments such as debridement and antiseptics reduce surface biofilm burden but rarely achieve full eradication. Emerging approaches include quorum sensing inhibitors, bacteriophage therapy, matrix-degrading enzymes, electroceutical dressings, antifungal strategies, and nanotechnology. They show promise when integrated with standard wound care. Conclusions: Biofilms are central to the pathogenesis of chronic wounds, DFUs, and burns. Integrating mechanism-based antibiofilm therapies with standard care represents a key research priority to improve healing outcomes.
    Keywords:  antimicrobial resistance; biofilms; burn wounds; chronic wounds; debridement; diabetic foot ulcers; wound healing
    DOI:  https://doi.org/10.3390/jcm14217784
  7. Microbiology (Reading). 2025 Nov;171(11):
    Interpretation guidance for MHRA regulatory considerations for phage therapeutic products.
    Carmen Coxon, Elizabeth Bell, Evelien Adriaenssens, Jason Clark, Joe Edwards, Tas Gohir, Francesca Hodges, Josh Jones, Cath Rees, Annette Sansom, Darren Smith, Mark Sutton, Clare Trippett, Dann Turner.
      On 4 June 2025, the MHRA published 'Regulatory considerations for therapeutic use of bacteriophages in the UK'. This was in response to recommendations made by the House of Commons Science, Innovation and Technology Committee Inquiry into the 'The Antimicrobial Potential of Bacteriophages'. The MHRA Regulatory Considerations for phage therapeutic products (PTPs) outlines the relevant regulatory route and requirements to use PTPs as licensed or unlicensed medicines. While this guidance provides the necessary information, it is recognized that regulatory information can be inaccessible to academic and small- to medium-sized enterprise developers who are often unfamiliar with the language, terminology and location of such information. The MHRA, in consultation with the Innovate UK Phage Innovation Network, has therefore developed this interpretation to help PTP developers understand what the guidance is saying, and what evidence is required for regulatory assessment of a marketing authorization application. Examples have been included throughout to provide context and as an aid to understanding.
    Keywords:  critical quality attribute; personalized medicine; phage therapeutic products; regulation
    DOI:  https://doi.org/10.1099/mic.0.001613
  8. FEMS Microbiol Rev. 2025 Nov 08. pii: fuaf057. [Epub ahead of print]
    Resistance to last-resort antibiotics in enterococci.
    Zhaoxiang Lu, Ross S Mclnnes, Freya Allen, Kavita Gadar, Willem van Schaik.
      The genus Enterococcus comprises a diverse group of species, many of which are commensal members of the gut microbiota of humans and animals. The two most prominent species associated with humans, Enterococcus faecalis and Enterococcus faecium, have also emerged as prominent opportunistic pathogens causing a range of infections in hospitalised patients, including urinary tract infections, bloodstream infections and endocarditis. The rise of antibiotic resistance in enterococci undermines the efficacy of the treatment of infections, thus posing a significant public health risk. Enterococci readily acquire resistance to antibiotics through chromosomal mutations and the horizontal gene transfer of antibiotic resistance genes. This review offers a comprehensive examination of the mechanisms of antibiotic resistance among enterococci, with an emphasis on resistance to last-line antibiotics, including to glycopeptide antibiotics like vancomycin and teicoplanin, oxazolidinones (primarily linezolid), and daptomycin. Furthermore, we evaluate relevant candidates in the current development pipeline for antibiotics and discuss alternative strategies (phage therapy and immunotherapeutics) for the treatment and prevention of infections with multidrug-resistant enterococci. As enterococci rapidly adapt to novel conditions, including by developing resistance to new drugs and therapies, sustained research efforts are required to ensure the continuous development of treatment options for these important opportunistic pathogens.
    DOI:  https://doi.org/10.1093/femsre/fuaf057
  9. J Virol. 2025 Nov 10. e0163724
    Identification and characterization of a novel plaque-invisible lytic single-stranded RNA phage.
    Yuer Wang, Fengjuan Tian, Jinbei Zhang, Shan Xu, Mengzhe Li, Yigang Tong.
      The RNA phages offer promising applications in biotechnology, including vaccine development and drug delivery. However, their potential remains underexplored due to the limited number of known RNA phages, partly because conventional methods fail to identify plaque-invisible lytic phages that do not form plaques. Here, we introduced a novel method that combines RNA-inclusive metagenomic studies and quantitative reverse transcription-PCR (RMS-RT-qPCR) to identify and characterize active RNA phages from environmental samples. This study led to the discovery of a new active Qbeta-like phage, named Cute. Genomic analysis revealed that Cute is a new member of the Qubevirus genus. Although Cute does not form plaques, it can be observed to continuously release into the supernatant when co-cultured with the host by RT-qPCR detection. This discovery underscores the potential diversity of RNA phages in nature and the limitations of traditional culture-dependent techniques. Our findings suggest that RMS-RT-qPCR could aid in the discovery of active RNA phages with significant biotechnological applications.IMPORTANCEThe discovery and characterization of RNA phages might be historically constrained by traditional culture-based methods. Our study provides a powerful tool for identifying active RNA phages by combining RNA-inclusive metagenomic analysis with RT-qPCR. This method expands our understanding of the diversity and ecological roles of RNA phages, which are often overlooked in microbiome studies. This research highlights the importance of RNA phages in natural ecosystems and their potential applications in biotechnology and medicine, such as antimicrobial therapies and vaccine development. By expanding our understanding of RNA phage diversity, this study opens new avenues for their utilization in various fields, emphasizing the need for continued exploration of these versatile biological entities.
    Keywords:  RNA phage; RT-qPCR; identification; metagenomic
    DOI:  https://doi.org/10.1128/jvi.01637-24
  10. Bioinform Adv. 2025 ;5(1): vbaf188
    ProkBERT PhaStyle: accurate phage lifestyle prediction with pretrained genomic language models.
    Judit Juhász, Noémi Ligeti-Nagy, Babett Bodnár, János Juhász, Sándor Pongor, Balázs Ligeti.
       Motivation: Phage lifestyle prediction, i.e. classifying phage sequences as virulent or temperate, is crucial in biomedical and ecological applications. Phage sequences from metagenome or virome assemblies are often fragmented, and the diversity of environmental phages is not well known. Current computational approaches often rely on database comparisons that require significant effort and expertise to update. We propose using genomic language models (LMs) for phage lifestyle classification, allowing efficient direct analysis from nucleotide sequences without the need for sophisticated preprocessing pipelines or manually curated databases. We trained three genomic LMs (DNABERT-2, Nucleotide Transformer, and ProkBERT) on datasets of short, fragmented sequences. These models were then compared with dedicated phage lifestyle prediction methods in terms of accuracy, prediction speed, and generalization capability.
    Results: ProkBERT PhaStyle achieves accuracy comparable to, and in many cases higher than, state-of-the-art models across various scenarios. It demonstrates the ability to generalize to unseen data in our benchmarks, accurately classifies phages from extreme environments, and also demonstrates high inference speed.
    Availability and implementation: Genomic LMs offer a simple and computationally efficient alternative for solving complex classification tasks, such as phage lifestyle prediction. ProkBERT PhaStyle's simplicity, speed, and performance suggest its utility in various ecological and clinical applications.
    DOI:  https://doi.org/10.1093/bioadv/vbaf188
  11. J Wound Care. 2025 Nov 01. 34(Sup11): S42-S46
    Use of autologous whole blood clot for hard-to-heal diabetic foot ulcers: a case series.
    Emre Ozker, Selim Aydin.
       OBJECTIVE: Diabetic foot ulcers (DFUs) are a severe complication of diabetes, contributing significantly to patient morbidity, healthcare costs and amputations. Current treatment approaches often fall short in addressing the challenges posed by hard-to-heal (chronic) wounds. This study evaluates the efficacy of autologous whole blood clot (AWBC) therapy in treating hard-to-heal DFUs.
    METHOD: Patients with hard-to-heal DFUs who were unresponsive to previous treatments were included in this case series. Prior to AWBC application, the wounds underwent debridement and cleansing of the wound bed. For the treatment, 18ml of blood was drawn from the patients to create the clot placed on the wound. Patients were evaluated weekly for wound healing progress.
    RESULTS: AWBC treatment was initiated in 20 patients, resulting in an average wound size reduction of 59% (p<0.001). The mean number of applications per patient was 5.3±1.5. Adverse events included contact dermatitis in one patient and discontinuation by another due to slower-than-expected healing.
    CONCLUSION: The results of this case series underscore AWBC's potential to restore the wound healing cascade by mimicking the extracellular matrix and promoting re-epithelialisation, angiogenesis and macrophage phenotype transition. AWBC represents a promising, cost-effective solution for DFU management, particularly in patients with complex comorbidities.
    Keywords:  autologous whole blood clot; case series; chronic wounds; diabetic foot ulcer; hard-to-heal; wound; wound care; wound dressing; wound healing
    DOI:  https://doi.org/10.12968/jowc.2025.0003
  12. J Wound Care. 2025 Nov 01. 34(Sup11): S47-S56
    A comparative analysis of sharp debridement devices for biofilm management in hard-to-heal wounds: a clinical assessment.
    Andrew Rader, Jeffrey Niezgoda, Martha R Kelso, Sandeep Gopalakrishnan.
       OBJECTIVE: Hard-to-heal wound biofilms are increasingly recognised as a major barrier to healing, contributing to persistent inflammation, delayed re-epithelialisation, and reduced responsiveness to standard therapies. While traditional sharp debridement (TSD) is a standard treatment, its limitations include the need for specialised training, the potential for pain and bleeding, and degree-specific scope of practice restrictions. This study investigated a novel multifaceted, sharp debridement device as a potential addition to the current portfolio of debridement technologies.
    METHOD: This prospective study enrolled patients with hard-to-heal wounds, randomised equally to either multifaceted, sharp debridement (EZ-Debride, MDM Wound Ventures, US (EZD)) or TSD (scalpels/curettes). Biofilm presence and extent were assessed pre- and post-debridement using a modified Alcian blue wound blotting technique, graded on a 0-3 scale. Biofluorescent imaging (BFI) and provider clinical assessments allowed additional evaluation of the biofilm removal efficacy.
    RESULTS: The experimental cohort comprised 80 patients. Both EZD and TSD significantly reduced biofilm, as evidenced by decreased Alcian blue staining grades post-debridement (p<0.005 for both). However, EZD resulted in a significantly greater reduction in biofilm than TSD (85.0% versus 34.9%, respectively; p<0.0001). While BFI showed limited correlation with Alcian blue staining overall, in cases with positive pre-debridement BFI imaging results, EZD achieved a 100% reduction in bacterial fluorescence compared with 50% using traditional methods. Clinical assessment confirmed a higher rate of complete biofilm removal in the EZD group compared with the TSD group (60.0% versus 12.2%, respectively).
    CONCLUSION: This study demonstrated that the novel multifaceted, sharp debridement device, EZD, is a safe and effective tool for biofilm removal in hard-to-heal wounds, potentially surpassing TSD methods. EZD offers a less invasive, more efficient, and potentially less painful approach, suggesting its value in improving clinical wound management and patient outcomes. Further research should examine its impact on long-term healing and broader clinical applicability.
    Keywords:  bioburden; biofilm; biofluorescence imaging; debridement; hard-to-heal; wound; wound care; wound dressing; wound healing
    DOI:  https://doi.org/10.12968/jowc.2025.0074
  13. Trends Microbiol. 2025 Nov 08. pii: S0966-842X(25)00307-5. [Epub ahead of print]
    The hitchhiker's guide to cross-species DNA delivery.
    Kotaro Kiga, Rodrigo Ibarra-Chávez.
      Microbial hitchhikers are rewriting the rules of horizontal gene transfer. He, Patkowski, et al. reveal how phage satellites assemble chimeric infective particles that deliver DNA across species boundaries through 'tail piracy'. This discovery reframes microbial innovation and provides a blueprint for next-generation biotechnologies, achieving what phage engineering has long pursued.
    DOI:  https://doi.org/10.1016/j.tim.2025.10.014
  14. Biophys Rep. 2025 Oct 31. 11(5): 330-343
    Bacterial restriction-modification systems: mechanisms of defense against phage infection.
    Haoyang Kang, Ang Gao, Yalan Zhu.
      Bacteria have evolved various defense mechanisms against bacteriophage invasion, driven by a long-term evolutionary arms race. Among them, restriction-modification (R-M) systems, which protect bacteria by DNA restriction and modification, are prominent. R-M systems are categorized based on their DNA methylation mechanisms, restriction activities, and cofactor dependencies. Here, we review the molecular basis of R-M systems and the diverse strategies used by bacteriophages to evade these defenses. Furthermore, we highlight the co-evolutionary dynamics between R-M systems and phage countermeasures, providing insights into new approaches to combat bacterial resistance and pathogenicity. Beyond their defensive roles, the multifunctionality of R-M systems in broader biological and biotechnological contexts is also discussed.
    Keywords:  Anti-restriction; Bacteriophage; DNA Modification; DNA Restriction; R-M system
    DOI:  https://doi.org/10.52601/bpr.2025.240070
  15. Microbiol Spectr. 2025 Nov 12. e0143125
    Comparative genomics reveals diversity and taxonomic relationships among Clostridioides difficile phages.
    Mohimenul Haque Rolin, Shakhinur Islam Mondal, Daniyal Karim, Nurnabi Azad Jewel, Tahsin Khan, Mustafizur Rahman, Arzuba Akter.
      Clostridioides difficile is associated with life-threatening antibiotic-associated diarrhea, colitis, and toxin-mediated infections. While antibiotics are the primary treatment against C. difficile infections, increasing resistance necessitates alternatives. Bacteriophages and bacteriophage-derived proteins, such as endolysins, hold promise as potential solutions. Understanding phage biology at the genomic level is crucial for their therapeutic use. We conducted a comparative genomic analysis of 44 C. difficile phage genomes from public databases, examining both whole-genome and proteome levels and grouping them by shared protein content. Relationships within each group were observed, and core and highly conserved genes were identified. Using genome and proteome phylogeny, average nucleotide identity, and core gene identification, we proposed an updated taxonomic classification. Nine distinct clusters were identified, without any singleton. Cluster members exhibited similar genome architecture, genome sizes, GC content, number of coding sequences, presence of core genes, and high nucleotide identity. Additionally, we propose 23 new genera, three families, and the elevation of currently assigned genera to subfamilies. The lytic module proteins, endolysins, and holins were also characterized, revealing four distinct endolysin organizations with diverse domain architectures. Notably, the amidase_3 and LysM domains were highly conserved and subjected to purifying selection within the C. difficile phage genomes. Our extensive comparative analyses of C. difficile phage genomes provide valuable genomic insights into the current understanding of the phages. The taxonomic analysis could refine the classification scheme for these phages and facilitate the future categorization of newly isolated C. difficile phage genomes.
    IMPORTANCE: Clostridioides difficile is a significant healthcare concern due to its role in causing severe infections and its increasing resistance to antibiotics. Phages present a promising alternative to antibiotics for combating bacterial pathogens, including C. difficile. Our study is the first comprehensive comparative genomic analysis of C. difficile phage genomes. We analyzed all available C. difficile phage genomes and clustered them into genetically distinct groups based on protein sharing. We also propose major taxonomic revisions to facilitate the accurate classification of C. difficile phages. Additionally, we investigated the lytic module of these phages, revealing diverse endolysin organizations and strong purifying selection acting on the catalytic and cell wall binding domains. Our findings contribute valuable insights into the biology of C. difficile phages and provide a framework that can aid in the classification and genomic analysis of newly isolated C. difficile phages in the future.
    Keywords:  Clostridioides difficile; bacteriophage; comparative genomics; endolysins; taxonomic classification
    DOI:  https://doi.org/10.1128/spectrum.01431-25
  16. Int J Biol Macromol. 2025 Nov 07. pii: S0141-8130(25)09266-9. [Epub ahead of print] 148709
    Dextran based hydrogel wound dressing with cytocompatible, anti-protein and antibacterial properties for infected wound healing.
    Fang Shen, Xiaofeng Ding, Guomi Wang, Menghui Chen, Huan Shi, Yan Peng, Dequn Wu, Qilong Chen, Bin Li, Wencheng Jiang.
      Hydrogel wound dressings are a common strategy for cutaneous wound healing and show great potential in modern wound management. In this study, we present a material design strategy for the development of a multifunctional dextran-based hydrogel with excellent biocompatibility, adequate mechanical properties, antimicrobial properties and protection against protein adhesion. By modifying the chemical properties of the dextran-based hydrogel precursor, the preparation of hydrogels with different cross-linking densities was achieved, and the abundant three-dimensional pore network was shown to provide excellent solubility and high drug-loading properties. In addition, in vitro antimicrobial performance showed that the hydrogels were able to maintain their antimicrobial properties for up to six days. Furthermore, we verified that the hydrogel has excellent cytocompatibility and anti-protein adhesion properties through cell, anti-protein adsorption experiments and could be degraded without contamination under body fluid conditions. Finally, we verified that the hydrogel could significantly reduce wound healing time and effectively promote wound healing through an in vivo animal wound model. Therefore, dextran-based hydrogels are expected to be used as a novel biodegradable antimicrobial wound dressing in the medical field.
    Keywords:  Antibacterial; Biocompatibility; Dextran; Hydrogel; Wound dressing
    DOI:  https://doi.org/10.1016/j.ijbiomac.2025.148709
  17. J Plast Reconstr Aesthet Surg. 2025 Oct 30. pii: S1748-6815(25)00631-X. [Epub ahead of print]
    Unresolved challenges in wound healing: When science meets clinical need.
    Paul Martin, Jason K F Wong, Gus McGrouther.
      Tissue damage is a natural consequence of mankind's interactions with the physical environment and leads to activation of endogenous repair mechanisms. Wound treatments developed over centuries, although largely empirical, have been incorporated into routine clinical practice while awaiting evidence of their efficacy. Based on a revisited and updated discussion from a 2013 Gordon Research Conference between basic scientists and clinicians, we outlined current knowledge of wound repair, emphasising the unique roles of diverse cell types including neutrophils, macrophages, keratinocytes, fibroblasts, and other previously overlooked lineages such as adipocytes and melanocytes. Five key clinical challenges remain unsolved: hypertrophic and keloid scarring, burns, wound infections, and chronic wounds. For each challenge, we reviewed recent basic science insights that offer potential therapeutic avenues, such as the role of inflammatory signals and mechanical cues in scarring, neutrophil dysfunction in burns, influence of the wound microbiome on infection, and epigenetic changes in chronic wounds. Although significant progress has been made, these topics remain problematic. We concluded by highlighting emerging research areas, including the overlooked roles of the nerves, fascia and fat tissue, and lessons from cancer biology, which may provide further opportunities to develop innovative strategies for wound care. By fostering greater collaboration and targeting a deeper understanding of mechanisms with unique models, the pathway to accelerate the translation of new therapies to improve patient outcomes is hopeful.
    Keywords:  Basic science; Complex wounds; Keloids; Scarring; Wound healing; Wound infection
    DOI:  https://doi.org/10.1016/j.bjps.2025.10.039
  18. Adv Exp Med Biol. 2026 ;1492 605-624
    Evaluating the Impact of Clear Dental Aligners on Dental and Periodontal Conditions, Oral Microbial Patterns, and the Immune System.
    Saharnaz Esmaeili, Soheil Shahbazi, Heliya Ziaei, Farnaz Younessian.
      Clear aligner therapy (CAT) has gained widespread adoption for managing malocclusions, primarily due to its aesthetic advantages, improved access for hygiene, and enhanced patient comfort relative to fixed appliances (FAs). However, CAT introduces a distinct intraoral environment that can influence microbial composition, biofilm development, and host immune responses. This chapter explores the effects of clear aligners on dental and periodontal health, oral microbial communities, and immunological parameters. Evidence indicates that CAT may facilitate plaque and biofilm accumulation, particularly on composite attachments, thereby increasing the risk of white spot lesions (WSLs), gingivitis, and dental caries. Despite these risks, aligners are generally associated with lower levels of pathogenic bacteria compared to FAs. Microbiome analyses of subgingival plaque and saliva reveal shifts in bacterial genera and phyla, although these changes are frequently non-pathogenic. CAT has demonstrated minimal negative effects on clinical periodontal indices, including the plaque index and gingival bleeding index, particularly when effective oral hygiene is maintained. Furthermore, aligners may reduce sustained immune activation by limiting plaque retention and aseptic inflammation, potentially decreasing the expression of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α. Although hypersensitivity reactions to aligner materials are infrequent, they warrant consideration. Overall, CAT appears to support periodontal health and promote a more stable oral microbial environment compared to FAs. Continued patient adherence to hygiene protocols and further long-term studies are necessary to fully evaluate systemic implications and optimize clinical outcomes.
    Keywords:  Clear aligner therapy (CAT); Dental biofilm; Immune response; Oral microbiome; Orthodontics; Periodontal health
    DOI:  https://doi.org/10.1007/978-3-032-03176-1_29
  19. FEMS Microbes. 2025 ;6 xtaf014
    Deciphering shared receptor usage in genomically unrelated bacteriophages infecting hypervirulent Klebsiella pneumoniae K1 ST23.
    Zhanybek Selpiev, Sebastian Leptihn, Mathias Müsken, Belinda Loh.
      Klebsiella pneumoniae is a critical pathogen often associated with multidrug resistance and hypervirulence. We report the isolation and characterization of three distinct lytic bacteriophages-Spear, Loop, and Shorty-from sewage, using a hypervirulent, hypermucoid K. pneumoniae K1 ST23 strain as the host. Despite genomic and structural differences, all three phages exhibited a narrow host range, infecting only the K1 serotype. Transmission electron microscopy and genomic analyses confirmed their lytic lifestyle and classifications: Spear and Loop are siphovirus-like, while Shorty is podovirus-like. A key focus was phage-host interaction and receptor usage. DNA sequence analysis showed no homology between the receptor-binding proteins, yet structural modelling revealed high similarity between Loop and Shorty tail fibers, aligning within a K1-specific lyase domain, suggesting phage genetic mosaicism. All three phages rely on capsular polysaccharide (CPS) for infection. Resistance selection under phage pressure yielded non-mucoid mutants, characteristic of CPS loss. Cross-resistance and adsorption assays confirmed CPS-dependence. Loop and Shorty showed near-complete loss of binding; Spear retained partial binding, suggesting additional receptors. These results highlight that unrelated phages can target the same bacterial structure, CPS. This has important implications for rational phage cocktail design, as CPS mutations may undermine seemingly diverse phage combinations.
    Keywords:  Klebsiella pneumoniae ST23; bacteriophage; capsular polysaccharide (CPS); genetic mosaicism; host–phage interaction; tail fiber structural homology
    DOI:  https://doi.org/10.1093/femsmc/xtaf014
  20. ACS Appl Bio Mater. 2025 Nov 11.
    Magnesium-Loaded Collagen/Hyaluronic Acid-Catechol Hydrogel Cross-Linked by Visible Light for Infected Wound Healing.
    Yu-Jin Kim, Yerim Song, Goeun Choe, Jin Yoo, Jonghoon Choi, Youngmee Jung.
      Skin, as the outermost barrier of the body, is highly vulnerable to wounds and injuries. Without timely and proper treatment, such wounds are prone to bacterial infection, which significantly impedes the healing process. As bacterial infection delays the wound healing process, effective control is critical for facilitating prompt tissue regeneration. However, conventional wound dressings generally lack intrinsic antibacterial activity, and commonly used antimicrobial agents─such as inorganic compounds or antibiotics─may cause systemic toxicity and contribute to antibiotic resistance. In this study, we designed a visible light-cross-linked collagen-based hydrogel incorporated with magnesium ions (Mg2+) to impart antibacterial functionality. The Mg2+-loaded hydrogel exhibited excellent biocompatibility, strong tissue adhesion, and significant antibacterial activity, achieving approximately 70% inhibition against Staphylococcus aureus as determined by the bacterial viability assay. Furthermore, in a full-thickness skin defect mouse model, the Mg2+-loaded composite hydrogel effectively suppressed bacterial growth and accelerated wound healing. This Mg2+-loaded collagen-hyaluronic acid hydrogel represents a promising therapeutic platform for infected wound treatment by integrating antibacterial efficacy, tissue adhesion, and enhanced regenerative potential.
    Keywords:  antibacterial; collagen-hyaluronic acid-based hydrogel; infected wound; magnesium; wound healing
    DOI:  https://doi.org/10.1021/acsabm.5c01725
  21. Acta Biomater. 2025 Nov 07. pii: S1742-7061(25)00829-3. [Epub ahead of print]
    From passive to active: Next-generation mechanically active dressings for wound healing.
    Pengfei Zhang, Zhengjiang Liu, Hailiang Pei, Akhlaq Ahmed, Yan Wei, Di Huang.
      Traditional passive dressings significantly slow down the wound healing process due to their lack of mechanical adaptability that matches human tissues. In contrast, mechanically active dressings (MADs), as a form of active intervention, can accelerate wound closure through their own mechanical deformation and are considered a key direction for next-generation wound care. Despite the continuous emergence of high-performance MADs in recent years, the relationship between their structural design characteristics and stimulus-responsive capabilities remains a major challenge that urgently needs to be addressed. In this review, the fundamental design principles governing MADs' function are first elaborated, followed by a thorough examination of the biomechanical mechanisms by which they promote wound healing. Next, the connection between material design and stimulus-responsive mechanisms is examined, followed by the highlighting of recent MADs breakthroughs and an outline of current limitations. Finally, the main challenges and solutions for translating these innovations into clinical practice are explored, providing new references for creating smarter dressings of the future. STATEMENT OF SIGNIFICANCE: This review addresses a critical gap in the field of mechanically active dressings (MADs) by moving beyond traditional single-material discussions to establish a unified design framework. This framework systematically links material morphology to diverse stimuli-responsiveness, including temperature, enzymes, ions, and magnetic fields. Furthermore, the introduction of a comprehensive performance comparison table transforms the review from a passive summary into a practical decision-support tool. Most importantly, by exploring patient-specific needs and commercialization pathways, we bridge the crucial gap between fundamental research and clinical practice, providing a clear roadmap for the rational design of next-generation wound care solutions.
    Keywords:  Biomechanics; Mechanically active dressings; Smart response; Wound healing
    DOI:  https://doi.org/10.1016/j.actbio.2025.11.010
  22. Adv Exp Med Biol. 2026 ;1492 101-120
    The Oral Microbiome, Oral Hyperpermeability, and Periodontitis in Metabolic Syndrome.
    Amine Nehaoua, Amin Gasmi, Sadaf Noor, Asma Gasmi Benahmed.
      The links between the oral microbiome, oral hyperpermeability, periodontitis, and metabolic syndrome (MetS) are good examples of the oral-systemic health connection. The oral microbiota is involved in host defense and metabolism. Oral dysbiosis disrupts periodontal homeostasis, increases the permeability of the oral mucosa, and triggers systemic inflammation, thus leading to MetS. On the other hand, metabolic disorders can change the environmental conditions in the oral cavity and exacerbate dysbiosis and periodontitis. Oral hyperpermeability is evidently a key player in this oral-systemic connection, allowing passage of oral bacteria, their by-products, and inflammatory mediators into the systemic circulation. It triggers the low-grade, chronic inflammation commonly seen in MetS and may exacerbate insulin resistance and other metabolic changes. Thus, periodontitis-a chronic inflammatory disease-is both a result and a cause of MetS. The classification of periodontitis as both a diagnostic marker and a treatment target in metabolic risk enhances the opportunity for the assessment and control of MetS. New-generation therapies targeting oral permeability and dysbiosis, such as barrier-strengthening agents, precision probiotics, and advanced antimicrobial agents, are potential strategies to address the oral-systemic health link. The concept of oral-systemic healthcare, incorporating both dental and medical care, is an emerging model of care delivery systems. Such strategies, including salivary risk management (SRM), targeted interventions, and patient education, may contribute to the enhancement of general health, particularly among individuals with or at risk of MetS.
    Keywords:  Metabolic syndrome; Oral hyperpermeability; Oral microbiome; Oral–systemic health; Periodontitis
    DOI:  https://doi.org/10.1007/978-3-032-03176-1_6
  23. Sci Adv. 2025 Nov 14. 11(46): eadx0790
    Cryo-EM structure of bacteriophage Bas63 reveals structural conservation and diversity in the Felixounavirus genus.
    James Hodgkinson-Bean, Rafael Ayala, Klemens McJarrow-Keller, Léna Cassin, Georgia L Rutter, Alexander J M Crowe, Matthias Wolf, Mihnea Bostina.
      The BASEL phage collection was developed to provide access to diverse bacteriophages, distinct from model phages. Escherichia phage JohannRWettstein (Bas63), a myophage in the collection, is a member of the subfamily Ounavirinae and the Felixounavirus genus. Using cryo-electron microscopy, we investigated Bas63's structure to explore its evolutionary relationships and functional adaptations. Our structures reveal a series of gene products: (i) a capsid decorated with β-tulip proteins at three-fold symmetry axes and a Hoc-like protein at hexamer centers, (ii) a conserved connector with an additional 12-fold ring of collar proteins that extend unique whisker proteins that are structurally related to podophage GP4 tail fibers, and (iii) a baseplate with long tail fibers resembling a contracted form of T4's long tail fibers. Sequence conservation analysis of Bas63 structural proteins across ICTV-recognized Felixounavirus' supports its role as a structural model for Felixounavirus evolution. This study advances the mechanistic understanding of phage architecture and reinforces the structural mosaicism of bacteriophages.
    DOI:  https://doi.org/10.1126/sciadv.adx0790
  24. Adv Emerg Nurs J. 2025 Oct-Dec 01;47(4):47(4): E7-E25
    Wound Assessment and Management: Key Concepts in Laceration Repair.
    Pedro A Colio, Michael D Gooch, Karen Sue Hoyt, Ann E Gerhart.
      The purpose of this article is to discuss wound assessment and management for advanced practice registered nurses (APRNs). Skin anatomy is reviewed, and the stages and methods of wound healing are also addressed. Common types of wound/skin disruption are listed. The importance of a thorough and meticulous history and physical exam outlining the appropriate initial evaluation of wounds and including the identification of potential complications such as infection, retained foreign bodies, and neurovascular injuries are also considered. Clinical decision-making and the formulation of differential diagnoses for patients presenting with wounds will be discussed along with a management plan for patients requiring laceration repair. Information regarding the procedural phase of care [e.g., anesthesia use, common wound closure techniques (e.g., suture, tissue adhesives, staples)], offering guidance on technique selection based on wound characteristics and location will also be given. A comprehensive plan of care including patient disposition, and referral and documentation exemplars with practical pearls to avoid litigation will also be provided. APRNs will also be offered evidence-based strategies to deliver safe and effective wound care and management.
    Keywords:  APRN; corner suture; interrupted suture; local anesthetics for wound repair; medical staple closure; tissue adhesive closure; vertical mattress suture
    DOI:  https://doi.org/10.1097/TME.0000000000000598
  25. J Wound Care. 2025 Nov 01. 34(Sup11): S15-S24
    Application of a full-thickness placental allograft in complex wound management: a case series across diverse aetiologies.
    Kirk Mitchell.
       OBJECTIVE: Management of complex hard-to-heal (chronic) wounds presents a substantial challenge in various healthcare settings where logistical constraints and patient-related factors can impede wound closure. This retrospective study evaluates outcomes associated with the use of a dehydrated, full-thickness placental allograft (CompleteFT; ExtremityCare, LLC, US) composed of the amnion, chorion and intermediate layers, when applied to complex hard-to-heal wounds in a mobile care environment.
    METHOD: A retrospective analysis reviewed data collected between February 2024 and July 2025 from patients (aged ≥18 years) with complex hard-to-heal wounds. Data were retrieved from a single mobile wound care service provider team (Compassionate Care Concierge, US). Prior to allograft application, all wounds exhibited stalled healing for at least 30 days with standard of care (SoC). The allograft was applied to all wounds as an adjunct to SoC. Trend changes in wound surface area and percentage area reduction (PAR) across various wound aetiologies were assessed, with additional endpoints including the number of allograft applications and relevant patient parameters.
    RESULTS: The patient cohort (n=114, with a total of 184 hard-to-heal wounds), included 51 males and 63 females, with a mean age of 73.1 years. Analysis revealed statistically significant PAR values for various wound aetiologies, such that: p<0.0001 for diabetic foot ulcers (n=11); venous leg ulcers (n=48); pressure ulcers (n=73); and wounds classified as 'other' (n=39). Surgical wounds (n=13) demonstrated a p<0.0007. The study allograft was well-tolerated, with no adverse events directly attributable to the product.
    CONCLUSION: Application of the full-thickness allograft as an adjunct to SoC presents a promising option for supporting wound size regression in complex, hard-to-heal wounds.
    Keywords:  CompleteFT; amniotic membrane; chronic wounds; complex wounds; full-thickness membrane; hard-to-heal; placental allograft; wound; wound care; wound closure; wound covering; wound dressing
    DOI:  https://doi.org/10.12968/jowc.2025.0459
  26. mBio. 2025 Nov 12. e0234125
    A synthetic gut microbiota provides an understanding of the maintenance and functional impact of phage.
    Heejung Koo, Kerim Heber, Shuchang Tian, Shane T Connolly, Fuhua Hao, Jingcheng Zhao, Bethany Swencki-Underwood, Andrew D Patterson, Guy E Townsend, Jordan E Bisanz.
      Phages are under intense study as therapeutics and mediators of microbial community behavior; however, tractable models are needed to study phages in the context of the mammalian gut. To address this gap, we isolated phages against members of a synthetic gut microbial community (sFMT), identifying the Bacteroides uniformis JEB00023 (DSM 6597) phage HKP09. While resistance to HKP09 was observable within hours of infection in monoculture, high titers of HKP09 were maintained in vitro and in gnotobiotic mouse models over extended periods. Sequencing of resistant B. uniformis lines revealed phase variation upstream of a capsular polysaccharide locus driving the generation of resistant and sensitive subpopulations, thus demonstrating a mechanism allowing stable coexistence of both virus and bacterial host. Communities infected in vitro and in vivo with HKP09 showed transiently reduced loads of B. uniformis DSM 6597. Its impact in the gut was distinct from communities constructed without its host B. uniformis strain (sFMT∆JEB00023). Rather than a compensatory increase in closely related Bacteroides strains, the most significant impacts were observed on distantly related strains, demonstrating that phage perturbations more broadly impact community structure in ways not easily predicted by phylogeny or simple strain exclusion. Metabolomic analyses of the feces of HKP09-infected sFMT-colonized gnotobiotic animals demonstrated altered abundances of amino acids and microbial fermentation products compared to uninfected mice and those colonized with sFMT∆JEB00023. Taken together, these data provide a controlled model for studying phages in the context of the mammalian gut, providing mechanistic insights into phage-host dynamics and their consequences on the function of microbial communities.
    IMPORTANCE: Phages are key members of the gut microbiome, but the understanding of their biological significance for host health lags behind their bacterial hosts. In this study, we demonstrate the use of a phage-infection model using defined, synthetic microbial communities that colonize the intestinal tract of mice. We uncovered that spontaneous inversions in the genome of Bacteroides uniformis perpetually generate subpopulations, which are either sensitive or resistant to phage infection, allowing for the coexistence of predator and prey in this species. Phage infection demonstrated broad impacts on community structure and metabolism in animals, which are not easily predicted by the exclusion of the viral host. This research demonstrates a tractable approach through which the impacts of phage on both the microbiome and mammalian host can be deciphered.
    Keywords:  bacteriophages; gnotobiotics; gut microbiome; metagenomics; synthetic communities
    DOI:  https://doi.org/10.1128/mbio.02341-25
  27. Diagnostics (Basel). 2025 Nov 03. pii: 2784. [Epub ahead of print]15(21):
    The Oral-Gut-Systemic Axis: Emerging Insights into Periodontitis, Microbiota Dysbiosis, and Systemic Disease Interplay.
    Amani M Harrandah.
      The oral cavity harbors one of the most diverse microbial ecosystems in the human body, second only to the gut. Periodontitis, a chronic inflammatory disease arising from oral microbiota dysbiosis, has been increasingly associated with systemic disorders such as diabetes mellitus, atherosclerosis, rheumatoid arthritis, inflammatory bowel disease, and neurodegenerative conditions. Although hematogenous dissemination of oral pathogens and inflammatory mediators has long been proposed as a mechanistic link, emerging evidence identifies the oral-gut axis as a novel bidirectional pathway. Swallowed oral pathobionts, such as Porphyromonas gingivalis and Fusobacterium nucleatum, can colonize the gut, disrupt the intestinal barrier, and induce dysbiosis, immune imbalance, and metabolic alterations that aggravate systemic inflammation and disease progression. In contrast, gut dysbiosis, especially in obesity or high-fat-diet models, can exacerbate periodontal tissue destruction through hyperuricemia, altered bone metabolism, and Th17/Treg immune imbalance. Experimental and clinical studies further support this reciprocal relationship, implicating microbial, metabolic, and immune crosstalk in both oral and systemic pathology. Understanding this oral-gut-systemic axis offers a paradigm shift in diagnostics and therapeutics, focusing on precision interventions such as microbiome modulation, probiotics, and integrated oral care to mitigate systemic inflammatory burden and improve overall health outcomes.
    Keywords:  gut dysbiosis; oral microbiota; oral-gut-dysbiosis; periodontal bacteria; periodontitis; systemic diseases
    DOI:  https://doi.org/10.3390/diagnostics15212784
  28. Cureus. 2025 Oct;17(10): e94362
    The Role Played by Imidazole Propionic Acid in Modulating Gut-Heart Axis and the Development of Atherosclerosis: An Explorative Review.
    Venkata BharatKumar Pinnelli, Jayashankar Ca, Venkataramana Kandi, Spandana P, Manish Gr, Mir Hyder Hussain, Akshay As, Kavitha R, Ramya Jp, Surendra Babu T, Sabitha Vadakedath.
      Recent studies have demonstrated the significant role of the normal human microbial component, also known as gut microbiome/gut microbiota (GM). Dysbiosis, or imbalance of GM, can predispose to systemic diseases, including cardiovascular disease (CVD). The GMs' influence extends further to cardiometabolic health, with microbial metabolites playing a pivotal role in these interactions. Traditional risk factors like hyperlipidemia and hypertension are now complemented by emerging evidence implicating GM-derived metabolites in the pathogenesis of atherosclerosis (ATS). Imidazole propionic acid (ImP), a metabolite of histidine derived from GM, has emerged as a significant mediator linking GM dysbiosis to ATS and CVD, or coronary artery disease (CAD). This comprehensive review synthesizes current knowledge on ImP's biosynthesis, molecular mechanisms, clinical relevance, and therapeutic potential, emphasizing its role in the gut-heart axis and cardiovascular pathology. Appropriate keywords, including "microbes", "dysbiosis", "gut microbiota/gut microbiome and cardiovascular disorders", "atherosclerosis and microbes", and "microbial metabolites", among others, were used to extract relevant studies in PubMed and Google Scholar from inception to date. ImP bridges microbial dysbiosis and CVD through endothelial dysfunction, inflammation, and metabolic disturbances. Its production is modifiable by diet and GM composition, positioning ImP as both a biomarker and therapeutic target in ATS and heart failure. Advancing understanding of ImP's biology and clinical impact will enable novel interventions to reduce the global burden of atherosclerotic cardiovascular disease (ASCVD), marking a change in basic assumptions in cardiovascular medicine centered on the gut-heart axis.
    Keywords:  atherosclerosis; biomarker; cardiovascular disease; coronary artery disease; dysbiosis; gut microbiome; gut microbiota; gut-heart axis; imidazole propionic acid; therapeutic target
    DOI:  https://doi.org/10.7759/cureus.94362
  29. Expert Opin Drug Deliv. 2025 Nov 14. 1-21
    Emerging landscape of bioinformatics and artificial intelligence applications in cell-penetrating peptide-based delivery.
    Yu Sun, Muqing Zhang, Huiting Liu, Hu Wang.
       INTRODUCTION: Peptides play diverse roles in biological processes, including drug discovery, antibacterial activity, and protein-protein interactions, making peptide prediction a crucial field. The development of bioinformatics tools has significantly enhanced our ability to study and harness peptide potential. Among these, cell-penetrating peptides (CPP) are a unique class of polypeptides capable of crossing cell membranes, facilitating the intracellular delivery of therapeutic agents such as small molecules, peptides, proteins, and nucleic acids. This ability has expanded possibilities in drug delivery, gene therapy, and molecular imaging. However, identifying and designing effective CPP remains challenging.
    AREAS COVERED: In recent years, various computational tools and algorithms have been developed to predict the cell-penetration potential of peptides, aiding in the discovery of novel CPP and accelerating their applications. This review provides a comprehensive overview of bioinformatics tools including artificial intelligence (AI) for peptide prediction, with a particular focus on CPP. Systematic literature search was performed from PubMed, Embase, Scopus, and the Web of Science to cover published references related to the current topic from 2011 to October 2025.
    EXPERT OPINION: Understanding their functions and limitations will help researchers make informed decisions and effectively utilize peptide prediction in diverse scientific and clinical applications.
    Keywords:  Peptides; artificial intelligence; bioinformatics; cell penetrating peptides; drug delivery
    DOI:  https://doi.org/10.1080/17425247.2025.2587940
  30. Front Pharmacol. 2025 ;16 1625595
    Factors affecting the effectiveness and safety of colistin in treating drug-resistant gram-negative bacterial infections: a meta-analysis.
    Pengfei Li, Shiran Li, Jiao Zhang, Siyu Zeng, Zhimin Li, Jinxian Xie, Yong Yang.
       Purpose: As an important antibiotic for treating infections caused by drug-resistant Gram-negative bacteria, colistin's clinical efficacy and safety might be influenced by multiple factors. This meta-analysis aimed to identify the key factors affecting the effectiveness and safety of colistin in treating these infections. The results of this study provide a reference for clinicians to choose treatment methods. At the same time, the rational use of colistin can prevent the occurrence of adverse drug reactions (AKI), improve the cure rate of patients, and delay the development of bacterial resistance.
    Methods: The overall mortality rate was designated as the primary effectiveness outcome, with clinical response rate and bacterial eradication rate serving as the secondary outcomes. The incidence of acute kidney injury (AKI) was evaluated as a safety endpoint. Key analytical variables included colistin dose (high-dose≥4.2 mg/kg/day and low-dose< 4.2 mg/kg/day), ACCI (low <5, moderate = five to six, high >6), co-therapy (carbapenems/tigecycline/fosfomycin, etc.), microbial species (Acinetobacter baumannii/Pseudomonas aeruginosa/Enterobacteriaceae, etc.), and administration methods (aerosolized plus intravenous colistin vs. intravenous colistin alone).
    Results: A total of 74 studies (N = 8,889 participants) were included in our analysis. Mortality was lower in the high-dose group compared to the low-dose group (34.09% vs. 41.08%, p = 0.09). In ACCI score subgroups (low, moderate, high), mortality rates were 27.11% vs. 44.69% vs. 47.11% (p < 0.01). Monotherapy was associated with a higher mortality rate compared to co-therapy (42.97% vs. 33.10%, p < 0.01). Although no statistical differences were observed among different pathogenic bacteria species, infection caused by A. baumannii exhibited the highest mortality rate at 43.75%. Mortality rates for aerosolized plus intravenous colistin versus intravenous colistin alone were 40.81% vs. 32.84% (p = 0.09). The incidence of AKI was significantly higher in the loading dose group, high-ACCI group, and group receiving concomitant nephrotoxic drugs while being notably lower in the Pseudomonas aeruginosa infection group.
    Conclusion: Loading dose, co-therapy (carbapenems or quinolones), microbial factors, and ACCI are the main factors associated with the effectiveness of colistin. Additionally, loading dose, microbial factors, ACCI, and co-therapy are associated with an increased risk of colistin-associated AKI.
    Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/search, identifier CRD420250655507.
    Keywords:  AKI; colistin; drug-resistant gram-negative bacteria; influencing factors; mortality
    DOI:  https://doi.org/10.3389/fphar.2025.1625595
  31. Gut Microbes. 2025 Dec 31. 17(1): 2575923
    Design and application of synthetic human gut microbial communities.
    Min Soo Kim, Jordan E Bisanz.
      The gut microbiome shapes host health through a complex network driven by both host‒microbe and microbe‒microbe interactions. Disruption of these interactions, often referred to as dysbiosis, is associated with a range of infectious and chronic diseases. Owing to the success of fecal microbiota transplantation (FMT) for the treatment of recurrent Clostridioides difficile infection, FMT has been explored as a therapeutic option for a range of microbiota-associated conditions, including inflammatory bowel disease and obesity. However, the microbial diversity that is the greatest strength of FMT is also its greatest liability. Concerns relating to reliance on human donors, potential for transmission of multidrug-resistant organisms or undesirable phenotypes demonstrate a need for alternate approaches, including the generation of synthetic alternatives to FMT, which can be built in the laboratory from individual strains. Furthermore, these communities are powerful tools for conducting mechanistic research allowing for the generation of 'knockout' communities, which are not possible when working with undefined fecal transplants. This review examines strategies for designing synthetic microbial communities that represent a new generation of microbiome-derived therapies. We highlight how synthetic microbial communities are being used to answer mechanistic questions about host-microbiome interactions relevant to health and disease. Finally, we examine the current clinical translation of these communities as live biotherapeutic products (LBPs). While the regulatory frameworks for LBPs continue to evolve, early clinical successes illuminate the potential for synthetic microbial communities to treat complex human diseases through targeted manipulation and restoration of the gut microbiome.
    Keywords:  Microbiome; cancer; colonization resistance; defined microbial consortium; dysbiosis; immunotherapy; infectious disease; inflammable bowel disease; live biotherapeutic products; synthetic community
    DOI:  https://doi.org/10.1080/19490976.2025.2575923
  32. Ann Biomed Eng. 2025 Nov 12.
    Sonic Serenity: Piezoelectric Nanomaterials Reshaping Wound Healing Paradigms.
    Jyoti Chandra, Garima Gupta, Khang Wen Goh, Prashant Kesharwani.
      Chronic wounds caused by infections pose a significant healthcare challenge due to the rise of antibiotic-resistant bacteria. Ultrasound-driven sonodynamic therapy (SDT) has emerged as a promising alternative, leveraging reactive oxygen species (ROS) for bacterial eradication. The integration of piezoelectric nanomaterials (NMs) with SDT (PSDT) enhances antimicrobial efficacy and accelerates wound healing by inducing electric stimulation. Recent studies highlight the potential of piezoelectric hydrogels and nanocomposites in promoting tissue regeneration. However, challenges remain in optimizing piezoelectric responses, ensuring biosafety, and improving ROS generation for clinical applications. Further research is essential to advance PSDT for effective bacterial-resistant wound treatments.
    Keywords:  Antibiotic resistance; Chronic wounds; Piezoelectric nanomaterials; Reactive oxygen species; Sonodynamic therapy; Wound healing
    DOI:  https://doi.org/10.1007/s10439-025-03909-6
  33. Lasers Med Sci. 2025 Nov 12. 40(1): 476
    Introducing biofeedback-integrated laser therapy: a novel approach for enhancing scar treatment.
    Waseem Jerjes.
      
    DOI:  https://doi.org/10.1007/s10103-025-04745-9
  34. J Wound Ostomy Continence Nurs. 2025 Nov-Dec 01;52(6):52(6): 503-509
    Use of Negative Pressure Wound Therapy in Selected Cases to Facilitate Abdominal Wound Healing: A Multiple Case Series.
    Karie Wilson, Terran Sims.
       BACKGROUND: Surgical wound dehiscence resulting in exposed bowel increases the risk for development of an enterocutaneous fistula. Consequently, management of exposed bowel in an open wound presents challenges in terms of wound care management. In addition, a surgical wound dehiscence within the peristomal plane of an ileal conduit also creates a complex challenge of maintaining an ostomy pouching system seal.
    CASES: Case 1 was a patient with peristomal skin complications requiring stoma re-siting and subsequent surgical wound dehiscence at the prior ostomy site. As a result, we addressed wound management in the setting of urinary leakage from the ileal conduit. We used negative pressure wound therapy (NPWT) in the setting of a peristomal dehisced surgical wound to promote healing and optimize peristomal skin health. Case 2 was a patient with an infected surgical incision requiring readmission to hospital and additional surgery. Intra-operative findings revealed a fascial defect with exposed bowel in the wound resulting in unique challenges for wound management. Again, we used NPWT in the setting of exposed bowel to promote granulation and achieve wound closure.
    CONCLUSION: Research regarding ideal wound management for complex open abdominal wounds with exposed bowel is sparse. These case studies summarize our clinical experience managing complex patients with wound dehiscence and abdominal fascia defects and risk of enterocutaneous fistula formation with NPWT.
    Keywords:  Exposed bowel; NPWT; Negative pressure wound therapy; Peristomal wound; Surgical wound dehiscence
    DOI:  https://doi.org/10.1097/WON.0000000000001233
  35. Med Sci Monit. 2025 Nov 09. 31 e949286
    A Review of Recent Advances in Fecal Microbiota Transplantation for the Treatment of Hepatic Encephalopathy.
    Junru Fang, Jian Fang.
      Hepatic encephalopathy (HE) results from a debilitating complication of liver cirrhosis and acute liver failure, characterized by neuropsychiatric abnormalities ranging broadly from mild cognitive impairment to respiratory failure to coma. The pathogenesis of HE is multifactorial, with gut-derived toxins, particularly ammonia, playing a central role. Recent advances in understanding the gut-liver-brain axis have revealed the importance of gut microbiota and dysbiosis in the development and progression of HE. Fecal microbiota transplantation (FMT), a clinical procedure that is performed to transfer fecal microbiota from a healthy donor to a patient with HE (recipient), has emerged as a promising therapeutic strategy for modulating gut microbiota and ameliorating HE. FMT facilitates the restoration of gut microbiota composition with increased microbial alpha diversity, reestablishment of the balance between beneficial and pathogenic bacteria, reduction in the production of gut-derived toxins, and improvement of intestinal barrier function. It also modulates immune and inflammatory responses, alleviating hepatocyte and biliary injury. FMT has also demonstrated efficacy in improving cognitive function and reducing hospitalizations in HE patients and can maintain a stable donor-like microbiota profile for up to 12 months post-transplantation. FMT is generally well-tolerated, with most adverse events reported to be mild and transient, providing a desirable option for HE treatment. This review provides a comprehensive overview of the current understanding of the role of gut microbiota in the pathogenesis of HE, the mechanisms underlying the therapeutic effects of FMT, and the clinical evidence supporting its use in HE. We will also discuss the limitations, challenges, and future prospects for FMT in the treatment of HE.
    DOI:  https://doi.org/10.12659/MSM.949286
  36. Wound Repair Regen. 2025 Nov-Dec;33(6):33(6): e70109
    Novel Wound Care Practices in Bullous Pemphigoid: A Systematic Review.
    Ted Jacoby, Danielle Yee, Ralina Karagenova, Joyce Chen, Roslyn Isseroff.
      Bullous pemphigoid is the most common autoimmune subepidermal blistering disease. Yet, despite its significant impact on patient morbidity and quality of life, the role of wound care in disease management is not well documented in the literature and there is an overall lack of consensus regarding optimal wound care strategies. This systematic review and meta-analysis aimed to critically appraise the available evidence on wound practices in bullous pemphigoid with the goal of identifying interventions that enhance clinical outcomes, including healing time, infection control, and pain management. A comprehensive literature review was performed on the National Institute of Health (Pubmed), Embase, and Web of Science. Two independent reviewers conducted the screening, with discrepancies resolved by consensus. Of 1087 total articles extracted, five articles met the inclusion criteria. Among them, two studies were eliminated due to their incomplete or terminated status, and three articles were included in this review, assessing ozone liquid dressing (OLD), recombinant human type XVII collagen (RHCXVII), and berberine-based dressings. OLD was associated with faster wound healing, decreased infection rates, and improved pain control. Application of RHCXVII hydrogel led to faster healing, blister regression time, and greater patient satisfaction. A single case of berberine 'stamp therapy' showed symptomatic benefit as a topical adjunct in bullous pemphigoid wound care. These findings highlight the emerging, yet underrepresented, role of wound care in bullous pemphigoid, as well as the need for large-scale, multicentre randomised controlled trials to critically evaluate wound care modalities in its management with the goal of constructing standardized guidelines.
    Keywords:  autoimmune blistering diseases; bullous pemphigoid; systematic review; topical therapy; wound care; wound dressings
    DOI:  https://doi.org/10.1111/wrr.70109
  37. Undersea Hyperb Med. 2025 Third Quarter;52(3):52(3): 279-282
    Hyperbaric Oxygenation Therapy as Adjunctive Treatment of Complex Wound Associated with Sterno-clavicular Septic Arthritis.
    Nandini Nukala, Rohini Rao, Denise Nemeth, Manjulatha Badam.
       Introduction: Sternoclavicular septic arthritis with pyomyositis is a relatively rare condition. While most cases of septic arthritis are caused by gram-positive organisms, such as Staphylococci and Streptococci spp., a small number of patients present with gram-negative organisms as the cause of their condition. Signs and symptoms can be non-specific, and although CT imaging aids in diagnosis, a timely identification relies primarily on a high index of clinical suspicion.
    Case Description: We present a case of a 44-year-old female patient with a history of poorly controlled diabetes mellitus who presented with a chronic, non-healing wound that developed on a background of non-traumatic sternoclavicular septic arthritis, chronic osteomyelitis of the clavicle and manubrium, and concomitant pectoralis pyomyositis caused by a gram-negative pathogen. The use of HBO₂ as an addition to this patient's treatment regimen hastened the healing process.
    Conclusion: Given the rarity of this condition, we consider that adding to the body of literature with regards to the diagnosis and treatment of this condition can help clinicians develop a keen eye for it, decreasing the morbidity and mortality associated with it.
    Keywords:   hyperbaric oxygen therapy; manubrial osteomyelitis; pectoralis pyomyositis; sternoclavicular septic arthritis; wound care; wound healing
  38. Sci Eng Ethics. 2025 Nov 13. 31(6): 34
    Compliance with Clinical Guidelines and AI-Based Clinical Decision Support Systems: Implications for Ethics and Trust.
    Éric Pardoux, Angeliki Kerasidou.
      Artificial intelligence (AI) is gradually transforming healthcare. However, despite its promised benefits, AI in healthcare also raises a number of ethical, legal and social concerns. Compliance by design (CbD) has been proposed as one way of addressing some of these concerns. In the context of healthcare, CbD efforts could focus on building compliance with existing clinical guidelines (CGs), given that they provide the best practices identified according to evidence-based medicine. In this paper we use the example of AI-based clinical decision support systems (CDSS) to theoretically examine whether medical AI tools could be designed to be inherently compliant with CGs, and implication for ethics and trust. We argue that AI-based CDSS systematically complying with CGs when applied to specific patient cases are not desirable, as CGs, despite their usefulness in guiding medical decision-making, are only recommendations on how to diagnose and treat medical conditions. We thus propose a new understanding of CbD for CGs as a sociotechnical program supported by AI that applies to the whole clinical decision-making process rather than just understanding CbD for CGs as a process located only within the AI tool. This implies taking into account emerging knowledge from actual clinical practices to put CGs in perspective, reflexivity from users regarding the information needed for decision-making, as well as a shift in the design culture, from AI as a stand-alone tool to AI as an in-situ service located within particular healthcare settings.
    Keywords:  Artificial intelligence; Clinical decision support systems; Clinical guidelines; Compliance; Design; Ethics; Trust
    DOI:  https://doi.org/10.1007/s11948-025-00562-z
  39. J Mater Chem B. 2025 Nov 12.
    Advances in hydrogels combined with photothermal/photodynamic therapy for bacterial infection.
    Zehui Xiao, Jifeng Liu, Zhiyong Song, Ting Du, Xinjun Du.
      Photoresponsive antimicrobial materials have emerged as critical biomaterials, celebrated for their remarkable efficacy in combating bacterial infections. Hydrogels, which consist of three-dimensional polymeric networks formed through physical interactions or covalent bonds, serve as an ideal platform for such applications. Recently, hydrogels with photoresponsive antimicrobial properties have garnered substantial attention in the field of infection control. These advanced hydrogels exhibit diverse and advantageous features, including exceptional water swelling capacity, superior oxygen permeability, high biocompatibility, facile drug loading and release capabilities, and structural versatility. Herein, we present a comprehensive review of the structures, properties, mechanisms of action, and drug delivery profiles of photoresponsive antimicrobial hydrogels. Furthermore, we discuss their potential biomedical and clinical applications and offer perspectives on future research directions in this rapidly evolving domain.
    DOI:  https://doi.org/10.1039/d5tb02001h
  40. Gut Pathog. 2025 Nov 10. 17(1): 86
    Progress and prospects of gut microbiota-targeted therapy for primary biliary cholangitis.
    Xuan Tang, Xin You.
      Primary biliary cholangitis (PBC) is a chronic cholestatic autoimmune disease. Current therapeutic options are limited, with some patients responding poorly to first-line treatment with ursodeoxycholic acid. However, second-line drugs are difficult to develop. There are no drugs available to treat liver dysfunction. Currently, the etiology of PBC is unknown, and the intestinal flora affects the liver through the gut‒liver axis. The hypothesis of intestinal dysbiosis has gradually been accepted and involves mechanisms such as leaky gut, abnormal bile acids metabolism, and dysregulated immune tolerance. We found that gut microbiota-targeted therapy, including antibiotics, dietary regulation, probiotic supplementation, and fecal microbiota transplantation, can effectively improve liver function, remodel the intestinal microbiota, and alleviate symptom. However, this therapy has limitations, such as large individual differences and unknown long-term efficacy and safety. Large-scale and long-term clinical studies are expected to promote the broad application of gut microbiota-targeted therapy in the clinic.
    Keywords:  Dietary regulation; Fecal microbiota transplantation; Intestinal microecology; Primary biliary cholangitis; Probiotic
    DOI:  https://doi.org/10.1186/s13099-025-00753-w
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