bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2025–10–26
27 papers selected by
Luca Bolliger, lxBio



  1. Mol Biol Rep. 2025 Oct 21. 52(1): 1051
      The global rise of multidrug-resistant (MDR) bacteria has rendered many antibiotics ineffective, posing serious threats to public health, agriculture, and environmental safety. In response, bacteriophage therapy has re-emerged as a precise, adaptable, and sustainable antimicrobial alternative. This review presents a comprehensive analysis of phage applications across medical, veterinary, agricultural, and environmental sectors. We examine phage-bacteria interactions, including life cycles, resistance mechanisms, and phage-derived enzymes that disrupt biofilms. Clinical studies demonstrate phage efficacy in treating chronic and MDR infections, especially in vulnerable populations. This review also highlights veterinary and agricultural uses, environmental sanitation, and food safety applications under One Health frameworks. Current challenges such as narrow host range, immunogenicity, and regulatory barriers are discussed alongside innovations in synthetic biology, nanotechnology-based delivery, and phage-antibiotic synergy. We emphasize the urgent need for standardized regulations, phage banks, and large-scale clinical trials to enable global adoption. Phage therapy offers a powerful complement to antibiotics and should be integrated into future antimicrobial strategies through sustained research, policy reform, and cross-sector collaboration.
    Keywords:  Antibiotics; Bacteriophage; Biofilm; Multidrug-resistant bacteria; Therapy
    DOI:  https://doi.org/10.1007/s11033-025-11173-z
  2. Microbiome Res Rep. 2025 ;4(3): 35
      The rising prevalence of multidrug-resistant (MDR) bacterial infections, coupled with the diminishing efficacy of antibiotics, has reinvigorated interest in bacteriophage (phage) therapy as a promising alternative, leveraging its unique bactericidal mechanisms and precise targeting capabilities. Concurrently, phage display technology has advanced tumor diagnostics and targeted drug delivery through high-throughput peptide screening. This review systematically evaluates the mechanisms, strategies, and clinical progress of phage-based applications in anti-infective and oncological therapies. Clinical evidence highlights its efficacy against respiratory, oral, wound, bloodstream, and urinary tract infections, alongside solid tumors. However, challenges persist, including limited host range, bacterial resistance, immunogenicity, inefficient delivery systems, and regulatory uncertainties. Future efforts should prioritize AI-driven phage optimization, standardized pharmacokinetic assessment, and interdisciplinary collaboration to accelerate clinical translation. Despite current limitations, phage therapy represents a transformative and scalable approach for combating antimicrobial resistance and advancing precision oncology, positioning it as a pivotal tool in addressing global health crises.
    Keywords:  Phage therapy; artificial intelligence; multidrug-resistant bacterial infections; phage display technology; tumor therapy
    DOI:  https://doi.org/10.20517/mrr.2025.31
  3. Proc Natl Acad Sci U S A. 2025 Oct 28. 122(43): e2523344122
      A renewed interest in bacteriophages has emerged from the explosive discovery of the complex pan-immune bacterial defense system and a revival of the therapeutic potential of phages in the age of widespread antimicrobial resistance to antibiotics. However, the road ahead is daunting because of the huge genetic diversity of phages and the vast numbers of genes of unknown function. A fully integrated approach that includes curiosity-driven exploration of phage biology, the development of integrated and inclusive research-education programs based on phage discovery and genomics (SEA-PHAGES), and the advancement of phage therapeutics provides a holistic structure for advancing the field. The phages of mycobacteria illustrate this model and a large mycobacteriophage collection reveals the enormous diversity of phages infecting a single bacterial strain and illuminates the evolutionary mechanisms giving rise to genomes with mosaic architectures. A set of 2,600 fully sequenced and annotated mycobacteriophage genomes and the development of tools for engineering them with desirable properties enable phage therapies for treating Mycobacterium infections for which antibiotics frequently fail. Technological advances in synthetic genomics and structural biology promise to rapidly advance this field and powerfully stimulate developments in all aspects of bacteriophage investigation and application. Here I describe what we have learned from the study of mycobacteriophages and how a holistic approach-integrating curiosity-driven research, inclusive education, and medicine-can serve as a model for advancing microbiology broadly.
    Keywords:  Mycobacterium; bacteriophage; genomics
    DOI:  https://doi.org/10.1073/pnas.2523344122
  4. BMC Microbiol. 2025 Oct 23. 25(1): 682
       BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa commonly leads to difficult-to-treat infections necessitating new therapeutics. Recently, bacteriophages have gained attention as promising alternatives. This study aimed to isolate, characterize virulent phages from various water sources against clinical carbapenem-resistant P. aeruginosa isolates to formulate a phage cocktail, and evaluate its in vivo efficacy using a mouse burn wound infection model.
    RESULTS: Biological and genomic characterization of isolated phages were determined by host range, temperature and pH stability, transmission electron microscopy analysis, and whole-genome sequencing. Three virulent phages without carrying antibiotic resistance, virulence or lysogeny-related gene included in the study and named as Baskent_P1_112 (Φ1), Baskent_P2_ICU (Φ2) and Baskent_P3_3B (Φ3). Φ1 exhibited podovirus-like morphology, while Φ2 and Φ3 displayed myovirus-like morphology. MOI values were determined as 100, 1, and 10, with corresponding burst sizes of 123, 288 and 115 PFU/CFU, respectively. All three phages were stable at temperatures between 4 and 50 °C; and pH 4-10, Φ1 and Φ3 were completely inactive at pH 2 and 12. Phages with diverse receptor binding site proteins exhibited complementary lytic activity profiles across different and overlapping sets of carbapenem-resistant P. aeruginosa isolates were used for formulation the phage cocktail thereby achieving a broad host range. The therapeutic efficacy of the phage cocktail was compared with antibiotic treatment in 45 Balb/c mice, divided into five groups. Blood and tissue samples were collected for CRP analysis, bacterial load, and histopathological examination. Wound surfaces were measured daily, and survival percentages were recorded.
    CONCLUSION: Compared to the untreated control group, phage therapy significantly reduced CRP levels and bacterial loads, enhanced wound healing, and improved survival rates without any toxicity. These results demonstrate that the formulated phage cocktail is a promising alternative treatment with a protocol adaptable for on-demand clinical use.
    Keywords:  Burn wound infection; Lytic phage; Phage cocktail; Phage therapy; Pseudomonas aeruginosa
    DOI:  https://doi.org/10.1186/s12866-025-04435-0
  5. Cureus. 2025 Sep;17(9): e92463
      Bacteriophage therapy is gaining increasing interest in the medical world due to the search for new treatments for bacterial infections in the era of antibiotic resistance. However, its use in the treatment of chronic rhinosinusitis (CRS) and infective endocarditis (IE) remains a challenge. Antimicrobial therapy with bacteriophages faces challenges such as the identification of the specific type of bacteriophage and the bacterium sensitive to it, the method of administration, and the safety of use. The aim of this paper is to review the available literature on the feasibility of bacteriophage therapy for CRS and IE, with a focus on its potential as an alternative or adjunctive approach to conventional antibiotic treatment. The analysis was based on articles available on the PubMed platform; original publications describing experimental trials investigating the potential efficacy of bacteriophages in the treatment of CRS and IE, published within the last 10 years, were selected for this review. Articles were searched using the following keywords: "phage therapy," "chronic rhinosinusitis," and "phage therapy infective endocarditis." A total of 54 articles were found, of which seven original papers were included in the review after reviewing the abstracts. Bacteriophage therapy has shown promising potential in the treatment of CRS and IE, but its clinical application remains limited by challenges such as the identification of susceptible bacterial strains, mode of administration, dosage, and safety of use. Future research must be done to unlock the full therapeutic potential of bacteriophage therapy for these indications.
    Keywords:  antibiotics resistance; bacteriophage therapy; bacteriophages; chronic rhinosinusitis; infective endocarditis
    DOI:  https://doi.org/10.7759/cureus.92463
  6. Annu Rev Microbiol. 2025 Oct;79(1): 497-522
      Bacteriophages (phages) are virtually ubiquitous and play a fundamental role in the ecological and evolutionary dynamics of their bacterial hosts. While phages are found across many thermal environments, they can be highly sensitive to changes in temperature. Moreover, phages are expected to face increasingly frequent and intense thermal perturbations with global climate change. In this review, we combine theoretical and empirical evidence to assess the impact of the thermal environment on phage biology at the global scale. We identify key thermal environments that phages inhabit, and we discuss the role of temperature in determining phage life-history strategies, ecological interactions, and evolutionary dynamics. We then explore the potential effects of thermal variation on phage functions in natural microbial communities and the application of phages as biomedical therapeutics.
    Keywords:  climate change; evolution; life history; phage; temperature
    DOI:  https://doi.org/10.1146/annurev-micro-042424-040029
  7. Microlife. 2025 ;6 uqaf028
      Phage therapy offers a promising strategy against bacterial pathogens in medicine and agriculture, but the rise of phage-resistant bacteria presents a significant challenge to its sustainability. Here, we used an environmental model bacterium, Pseudomonas protegens CHA0, to investigate phage resistance mechanisms in laboratory conditions through genomic analysis of four phage-resistant variants (C2, C4, C17, C18). Whole-genome sequencing revealed frequent deletions, insertions, and single nucleotide substitutions, particularly in genes encoding enzymes involved in cell surface modifications. The T428P mutation in AlgC, a phosphoglucomutase, and the P229T substitution in YkcC, a glycosyltransferase, each conferred resistance by altering phage receptor accessibility while preserving bacterial fitness. These findings emphasize that subtle mutations in surface-modifying enzymes enable P. protegens to evolve resistance to bacteriophages without compromising their ecological performance.
    Keywords:  Pseudomonas; Pseudomonas phage; bacterial variant; bacteriophage; phage; phage resistance
    DOI:  https://doi.org/10.1093/femsml/uqaf028
  8. ACS Omega. 2025 Oct 14. 10(40): 46704-46713
      Cystic fibrosis (CF) is a common genetic disorder that significantly reduces life expectancy, particularly among Caucasians. It is caused by mutations in the CFTR protein, leading to thick mucus secretions that encourage microbial colonization, particularly in the lungs. While Pseudomonas aeruginosa and Staphylococcus aureus are well-established contributors to CF lung infections, recent research highlights a more diverse range of pathogens, including Escherichia coli, which is not typically considered a respiratory pathogen. In this study, we identified and characterized four new bacteriophages with lytic properties specifically targeting multidrug-resistant Extraintestinal Pathogenic E. coli strains isolated from CF patients. Phages were isolated from wastewater samples and tested for their lytic activity against a panel of E. coli strains. A detailed analysis of their genomic and biological properties, including host range and stability under various temperature and pH conditions was conducted. Transmission electron microscopy provided further insights into phage morphology. These findings demonstrate the potential of phage therapy as an alternative treatment for antibiotic-resistant infections, especially in CF patients. As multidrug-resistant bacteria become increasingly prevalent, the discovery of novel bacteriophages offers a promising solution to combat these difficult-to-treat infections. Further research is required to explore their clinical applications.
    DOI:  https://doi.org/10.1021/acsomega.5c04140
  9. Food Microbiol. 2026 Mar;pii: S0740-0020(25)00199-6. [Epub ahead of print]134 104919
      Proteus mirabilis is an opportunistic pathogen belonging to the genus Proteus in the Morganellaceae. It is closely associated with infections of the gastrointestinal and urinary systems in humans and animals, posing a threat to the safety of food industries. With the increasing abuse of antibiotics, the problem of bacterial resistance has become extremely urgent. Moreover, animal-source foods often have drug residues, making it an urgent need to explore alternatives to antibiotics. Bacteriophages, bacteria-lysing viruses, cause no biological pollution and do not induce bacterial antibiotic resistance, making them potential green biological bactericides. In this study, 24 pathogenic P. mirabilis strains were isolated as host bacteria. Two virulent bacteriophages, Proteus phage ABTNL-P14 (referred to as P14) and Proteus phage ABTNL-Pp2 (referred to as Pp2), were isolated and identified, both showing effective infectivity against P. mirabilis. Two phages were confirmed as virulent strains lacking virulence factors, lysogeny-related genes and antibiotic resistance genes, meeting safety criteria for food applications. This study also evaluated the effectiveness of a P14 and Pp2 phage cocktail in eliminating P. mirabilis from chicken breast meat at 4 °C under MOIs of 1, 100, and 10,000. Notably, at a high MOI (10,000), the phage cocktail eliminated two host strains on chicken breast meat surfaces within 1 h and 6 h. Therefore, the phage cocktail has the potential to eliminate P. mirabilis in foods at low temperatures, serving as a green antibacterial agent for food applications.
    Keywords:  Bacteriophage; Food safety; Genome analysis; Phage cocktail; Proteus mirabilis
    DOI:  https://doi.org/10.1016/j.fm.2025.104919
  10. Sci Rep. 2025 Oct 24. 15(1): 37229
      The overuse of antibiotics in the aquaculture sector to prevent and treat the pathogen Edwardsiella tarda in striped catfish Pangasianodon hypophthalmus has led to the rapid emergence of multidrug-resistant (MDR) E. tarda isolates. Alternative strategies, such as phage therapy have been considered to control this MDR bacteria pathogen. We present here three lytic bacteriophages vB_EtA_WAG25P1, vB_EtA_WCT72P1, and vB_EtA_DT115P1 infecting E. tarda isolates, with their geographical origins from Mekong Delta, Vietnam. Morphological analyses combined with their genomic data indicate that the bacteriophages are classified to Autosignataviridae family in Autographivirales order. In the latent period of 35 min, the phage WCT72P1 and WAG25P1 had the burst size of about 45 virions and 61 virions per infected cell, respectively, while 51 virions were released in the shorter latent period of 25 min for the phage DT115P1. They also owned several prominent biological properties as the high species-specificity of infection, the effective in vitro repression of the MDR E. tarda growth for approximately four hours, pH resistance, and thermal stability. The phage WAG25P1 and DT115P1 exhibited the highest nucleotide identity to Klebsiella phage RCIP0053 with the sequence identity of 67.4% and 68.1%, respectively, while the phage WCT72P1 was closely related to Klebsiella phage RCIP0089 with the similarity of 66.6%. The phages were in a cluster of new species belonging to the new unassigned genus. The genome analysis also showed their safety due to the absence of the recombination, integration and host virulence genes. To the best of our knowledge, this is the first report of novel lytic phages infecting E. tarda isolates in striped catfish Pangasianodon hypophthalmus and it will also pave way for their potential applications for phage biocontrol of the disease in striped catfish.
    Keywords:   Edwardsiella bacteriophage; Edwardsiella tarda ; Bacillary necrosis of pangasius (BNP); Genome analysis; Multidrug-resistance (MDR)
    DOI:  https://doi.org/10.1038/s41598-025-20979-7
  11. NAR Genom Bioinform. 2025 Dec;7(4): lqaf134
      Viral taxonomy is a challenging task due to the propensity of viruses for recombination and the lack of universal gene markers. As a result, recent ICTV updates increasingly rely on multiple tools for taxonomic ranking, with a growing emphasis on proteome-based clustering approaches. At the same time, the rapid expansion of viral datasets presents new challenges in organizing, analysing, and discovering phage relationships at scale. To address these challenges, we introduce hierarchical viruses, a framework for comparative genomics of bacteriophages that leverages protein Language Model (pLM) embeddings to generate proteome-wide vector representations of phages. Clustering the vector representations of 24 362 phages from the curated INPHARED dataset reveals a multi-scale hierarchical organization of phages. This hierarchy aligns with current ICTV taxonomic rankings at the genus and subfamily levels, with an adjusted mutual information score greater than 0.9 for both, in the Herelleviridae family, demonstrating that pLM-based proteome representations can effectively capture evolutionary relationships without relying on multiple sequence alignments. The framework builds the basics towards vectorial phage datasets that encode evolutionary information, thus allowing discovery of phage relationships at scale.
    DOI:  https://doi.org/10.1093/nargab/lqaf134
  12. Sci Rep. 2025 Oct 21. 15(1): 36527
      Erwinia amylovora is the causative agent of fire blight. Resistance to streptomycin, the main antibiotic in fire blight management, has led to an urgent requirement to develop alternative biological control agents, such as the phage-carrier system (PCS). Previous studies have focused on the dynamic interactions between the carrier (Pantoea agglomerans), lytic phages, and the pathogen. However, crucial information about phage receptors on these hosts is still lacking. Here, a biochemical approach was used and the phage receptors of two E. amylovora phages (ϕEa21-4 and ϕEa46-1-A1) on both hosts, have been identified as LPS and OmpA on E. amylovora and OmpA only on P. agglomerans. Interestingly, this work uncovered for the first time that amylovoran is tightly attached to the LPS of E. amylovora. Confirmation of this interaction and an infection model are presented that have far reaching implications for additional PCS improvement and pathogen-host interaction details.
    Keywords:   Erwinia lytic phages; Pantoea agglomerans ; Fire blight; Lipopolysaccharides; Outer membrane protein A; Phage-carrier system; ϕEa21-4; ϕEa46-1-A1
    DOI:  https://doi.org/10.1038/s41598-025-15724-z
  13. Eur J Clin Microbiol Infect Dis. 2025 Oct 23.
       PURPOSE: Cutaneous botryomycosis is a chronic, granulomatous infection of the skin caused by different bacteria that form granular aggregates. We aim to provide a complete, comprehensive, and updated review of cutaneous botryomycosis, including a review of cases published in the last decade.
    RESULTS: Patients with botryomycosis typically present multiple nodules, sinuses, abscesses, fistulae, and ulcers, which develop during weeks or months. The current gold standard for diagnosing botryomycosis involves a combination of histopathological examination and microbial culture. A definitive diagnosis is established when clinical and pathological findings align with the presence of botryomycosis, supported by the identification of non-filamentous bacteria forming granules and positive culture. The most frequent isolated etiological agents are Staphylococcus aureus followed by Pseudomonas aeruginosa. The differential diagnosis includes mycetoma, actinomycosis, and carcinomas/sarcomas. Treatment includes antibiotics and, in selected cases, surgical debridement.
    Keywords:  Botryomycosis; Cutaneous botryomycosis; Cutaneous trauma; Pseudomycosis; Staphylococcus aureus; Staphylococcus sp.
    DOI:  https://doi.org/10.1007/s10096-025-05326-y
  14. Virus Res. 2025 Oct 18. pii: S0168-1702(25)00123-6. [Epub ahead of print] 199645
      Chlamydia trachomatis (C. t) is the most common causative agent of sexually transmitted bacterial urogenital infections worldwide. C. t treatment failure is increasing because antibiotic resistance has developed in recent years. Therefore, the development of novel therapeutic strategies is necessary. Here, we constructed an M13 phage carrying two functional peptides, including the integrin binding peptide arginine-glycine-aspartic acid (RGD) on pⅧ and the IN5 protein from Chlamydia caviae phage φCPG1 on pIII to reduce C. t infection. We called these phages M13-RGD8-IN53. The recombinant phages successfully expressed IN5 proteins. Confocal laser scanning microscopy confirmed that the recombinant phages were able to enter HeLa cells and C. t inclusion bodies. IN5 protein was responsible for the observed decrease in C. t infection, while RGD enhanced the permeability of phages into the cells. The M13-RGD8-IN53 phage was better than the M13-IN53 phage in ameliorating C. t infection. qPCR revealed that treatment with the recombinant phages downregulated several C. t genes related to virulence, such as CT_046 (Hc2), CT_443 (OmcB), CT_444 (OmcA), CT_456 (Tarp), CT_666 (Cdsf), CT_694, CT_743 (Hc1), and CT_875 (TepP). The only upregulated gene was CT_119 (IncA). The recombinant phages impacted the C. t mainly in the middle and late stages of the development cycle. Our results suggest that novel recombinant phages are promising as candidates to treat C. t infection.
    Keywords:  Chlamydia trachomatis; IN5; M13 phage; arginine-glycine-aspartic acid; inhibition; recombinant phage
    DOI:  https://doi.org/10.1016/j.virusres.2025.199645
  15. Iran J Biotechnol. 2025 Jul;23(3): e4018
      Advancements in nucleic acid therapeutics have opened new avenues for treating genetic diseases, with antisense oligonucleotides (ASOs) such as antisense RNA (as RNA) emerging as promising candidates. RNA medicine, targeting various RNA molecules, offers potential therapeutic interventions. RNA-based therapeutics encounter challenges like stability, delivery, and off-target effects. Advances in delivery systems, such as lipid and polymeric nanoparticles and virus-like particles, offer solutions to enhance efficacy. This review explores the mechanisms and applications of RNA therapeutics, focusing on antisense oligonucleotides. Several platforms like lipid nanoparticles, polymeric nanoparticles, cell-penetrating peptides, exosomes, polyplexes, and virus-like particles (VLPs) for antisense RNA delivery are utilized to overcome challenges such as RNA stability and intracellular delivery. The potential of bacteriophages and VLPs as versatile delivery systems for RNA therapeutics targeting bacterial infections, biofilm eradication, cancer therapy, and viral infections is explored. Utilizing bacteriophages for targeted antisense RNA delivery improves therapeutic outcomes. Bacteriophage systems are advantageous due to ease of development, large cargo capacity, ability to carry non-DNA payloads, and relative safety, making them effective nanocarriers. The review also highlights FDA-approved ASO drugs and CRISPR-derived approaches for antibacterial and antiviral therapy. Through an in-depth analysis of platforms, mechanisms, and applications, this review provides insights into the expanding landscape of RNA therapeutics and their clinical implications.
    Keywords:   Antisense RNA Delivery; Bacteriophage; RNA therapeutics; Therapeutic potential
    DOI:  https://doi.org/10.30498/ijb.2025.486953.4018
  16. RSC Med Chem. 2025 Oct 08.
      Antimicrobial resistance threatens global health, with multidrug-resistant pathogens causing millions of deaths annually. Conventional antibiotics face limitations due to bacterial biofilms, resistance mechanisms, and host toxicity. Bacteriophages, due to their high specificity, hold great potential in antimicrobial therapy, targeted drug delivery. In recent years, advances in chemical biology and nanomaterials science have led to the continuous refinement of surface chemical modification strategies for bacteriophage capsids, providing robust support for their functional expansion. This review summarizes commonly employed bacteriophage surface modification techniques, including both covalent and non-covalent approaches, and categorizes various types of photosensitizers along with their recent progress in antimicrobial applications. Furthermore, it highlights recent studies on bacteriophage-photodynamic synergistic therapy systems in treating bacterial infections and discusses their application prospects and future directions in the field of precision antimicrobial therapy.
    DOI:  https://doi.org/10.1039/d5md00669d
  17. Expert Rev Anti Infect Ther. 2025 Oct 24.
       INTRODUCTION: The community of microorganisms that colonize the intestine plays a vital role in regulating human metabolism and immune system function. According to translational medicine studies, administering antibiotics disrupts the balance of microorganisms in the gastrointestinal system, increasing the risk of multiple diseases. Dysregulation and reduction of the biodiversity of intestinal microbiota increase the risk of developing unhealthy conditions for the host. In this review, we tried to offer a current vision regarding the use of antibiotics and the modification of the intestinal microbiota.
    AREAS COVERED: Research has also shown that, in addition to antibiotics, the composition and balance of the intestinal microbiota depend on diet from the first days of life (breastfeeding or formula) and the mode of delivery (vaginal birth or cesarean section). Having this in mind, we performed an extensive literature search in PubMed, Scopus, Embase, and Web of Science on the relationships between human microbiota and antibiotics.
    EXPERT OPINION: Effective antimicrobial stewardship programs are urgently needed to reduce the misuse of antibiotics to avoid bacteria becoming more resistant, resulting in the ineffectiveness of antibiotics. Alternatives to antibiotics, e.g. targeted probiotics or bacteriophages, as a strategy to preserve the intestinal microbiota diversity and maintain a good health status.
    Keywords:  Gut microbiota; anti-infective therapy; antibiotics; antimicrobial resistance; dysbiosis; probiotics
    DOI:  https://doi.org/10.1080/14787210.2025.2579881
  18. Braz J Microbiol. 2025 Oct 24.
      The study was conceived with the objective to isolate and characterize lytic bacteriophages (phages) against Staphylococcus aureus (S. aureus) associated with bovine mastitis. Phages were isolated from enriched slurry and milk samples using the agar overlay technique. Characterization included plaque morphology, Field Emission Scanning Electron Microscopy (FE-SEM), pH and thermal stability, host range (spot assay), adsorption assay and one-step growth curve analysis. Lytic efficacy was assessed using the Efficiency of Plating (EOP) method. Five phages (pS1 to pS5) were isolated, of which pS4 and pS5 were temperate phages as indicated by its lysis pattern. The analysis showed that phages pS2 and pS3 produced clear, pinpoint-sized plaques while pS1 formed large, clear plaques. FE-SEM classified all three phages under the class Caudoviricetes. Adsorption assay and one step growth curve analysis revealed that the phages had an adsorption time ranging from 9 to 15 min, and a latent period between 30 and 50 min and burst sizes of 68 (pS2), 220 (pS1) and 280 (pS3) pfu/cell. Stability tests revealed significant difference in thermal stability at 60 °C and 70 °C (p < 0.0001), and in pH tolerance from pH 2 to 10 (p < 0.0001) among pS1, pS2 and pS3. The spot assay revealed that the complete panel of clinical S. aureus isolates (n = 18), standard cultures (ATCC 12600 and ATCC 29213) and clinical isolates of S. chromogenes and S. haemolyticus were sensitive to pS1. In contrast, pS2 and pS3 exhibited lytic activity exclusively against the S. aureus isolates, showing no activity against S. chromogenes or S. haemolyticus. Phage pS1 demonstrated good lytic effect against 10/21 test isolates compared to pS2 (3/21) and pS3 (3/21). Overall, the study characterized three lytic phages targeting S. aureus implicated in bovine mastitis and showed its in vitro efficacy against planktonic S. aureus.
    Keywords:   S. aureus ; Adsorption assay; EOP; FE-SEM; One step growth curve analysis; Phage
    DOI:  https://doi.org/10.1007/s42770-025-01793-9
  19. MedComm (2020). 2025 Nov;6(11): e70378
      Chronic wounds-such as diabetic foot ulcers (DFUs), pressure ulcers (PUs), and venous leg ulcers (VLUs)-pose a serious clinical challenge due to their prolonged inflammatory phase and impaired healing. Increasing evidence reveals that dysregulated immune responses are central to the pathogenesis of chronic wounds. A complex interplay between innate and adaptive immune cells, including macrophages, neutrophils, and T cells, contributes to chronic inflammation, extracellular matrix (ECM) degradation, and tissue repair failure. While current treatments target symptoms, they often overlook the underlying immunopathology. This review provides a comprehensive analysis of the immunomodulatory mechanisms governing chronic wound healing, emphasizing the distinct immune landscapes in DFUs, PUs and VLUs. It explores immunotherapeutic strategies including cytokine-based therapies, protease inhibitors, and biomaterials with immunoregulatory functions. Special attention is given to the emerging roles of mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (EVs) in modulating inflammation, promoting angiogenesis, and enhancing tissue regeneration. Recent clinical trials of these therapies are also critically evaluated to bridge preclinical findings with translational relevance. By integrating immunology, regenerative medicine, and clinical insights, this review highlights novel targets and strategies for immunomodulation, providing a valuable framework for advancing precision therapies in chronic wound care.
    Keywords:  EVs; biomaterials; chronic wound; clinical trials; immunomodulation; stem cells
    DOI:  https://doi.org/10.1002/mco2.70378
  20. Food Microbiol. 2026 Mar;pii: S0740-0020(25)00210-2. [Epub ahead of print]134 104930
      Campylobacter jejuni is a global major foodborne pathogen and the leading cause for gastrointestinal infections in the European Union, often associated with the consumption of contaminated chicken meat. Physical and chemical decontamination measures can negatively affect the organoleptic properties of raw chicken meat while bacteriophages, as biological approach, can specifically combat pathogenic bacteria and have virtually no impact on the sensory attributes of the food matrix. However, their mode of action usually requires the growth of the target pathogen. This study aimed to systematically investigate the impact of the conditions prevailing in packaged raw chicken meat, compared to the host's optimal growth conditions, on the antibacterial efficacy of a Campylobacter-specific phage. The flagellotropic bacteriophage B14 and its bacterial host Campylobacter jejuni PT14 were used to develop a liquid model system based on Mueller-Hinton broth, in which the parameters pH, atmosphere composition, temperature, and chicken meat juice concentration, as well as metal cations were adjusted and the effect on host growth as well as on the antibacterial efficacy of the phage was evaluated based on log ratios of C. jejuni PT14 counts. In general, the effectiveness of phage B14 treatment was significantly reduced when pH, atmosphere and temperature differed from optimum growth conditions of C. jejuni PT14 (pH 7 to 9; microaerobic; 42 °C). However, the influence on growth alone could not explain all effects on the antibacterial efficacy of the phage. The results show that conditions relevant for raw chicken meat storage are disadvantageous for the inactivation of C. jejuni PT14 by phage B14. These findings contribute to the understanding of the phage-host interaction and can support the optimization of the application concept of Campylobacter phages in poultry meat production.
    Keywords:  Bacteriophage; Campylobacter jejuni; Chicken meat juice; Food-related factors; Inactivation
    DOI:  https://doi.org/10.1016/j.fm.2025.104930
  21. Curr Pharm Biotechnol. 2025 Oct 20.
       INTRODUCTION: The current pharmaceutical industry has increasingly adopted artificial intelligence (AI), integrating it across the entire industrial chain. While AI improves efficiency and reduces costs, it also faces challenges. This study explores both the technological evolution and contemporary innovation hotspots of AI in pharmacy.
    METHODS: Methods: This study adopts a fusion analysis of multi-source data, constructing a bidimensional analytical framework based on patented inventions (1990-2024) and research articles (2020-2024) as research objects. The study applies the Latent Dirichlet Allocation (LDA) topic model to analyze the evolution of patent topics and employs CiteSpace to construct keyword knowledge graphs from research articles. By integrating patent and article data to define technical labels, the study identifies research hotspots from the perspective of the pharmaceutical life cycle, enabling cross-validation from both scientific and technical dimensions.
    RESULTS: The number of AI-related patents in the pharmaceutical field has grown rapidly over the past five years. Technological topics exhibit a distinct evolutionary trend. Research hotspots span the entire pharmaceutical life cycle, from drug development to clinical delivery. Additionally, potential directions for future technological development have been identified.
    DISCUSSION: Research hotspots in the application of AI in pharmaceuticals include target identification, virtual screening, drug delivery, clinical trials, and pharmacovigilance. Precision medicine and explainable AI (XAI)-driven pharmacy modeling are expected to emerge as key directions for future technological development.
    CONCLUSION: AI has already reshaped the pharmaceutical industry through applications across all stages of the pharmaceutical life cycle. It is poised to attract growing research attention and drive innovative applications in the years ahead.
    Keywords:  Artificial intelligence; knowledge graph; patents.; pharmaceutical life cycle; topic modeling
    DOI:  https://doi.org/10.2174/0113892010412180250930230046
  22. Eur J Microbiol Immunol (Bp). 2025 Oct 21.
      Staphylococcus aureus is a clinically important bacterial pathogen causing infections from superficial skin lesions to life-threatening systemic diseases. The emergence of methicillin-resistant S. aureus (MRSA) has compounded the global health burden, particularly in low- and middle-income countries, as its quorum-sensing (QS) mediated mechanisms contribute to its persistence, resistance, and evasion from host immune responses and antimicrobial treatments. Thus, these features compromise the effectiveness of conventional antibiotics, urging the need for alternative therapeutic approaches. To resolve these issues, several non-antibiotic antibiofilm approaches have been developed. Bacteriophages and phage-derived enzymes show promising specificity in lysing bacterial cells and disrupting biofilms. Antimicrobial peptides (AMPs), with their broad-spectrum activity, destabilize bacterial membranes and modulate immune responses. Monoclonal antibodies can neutralize toxins or inhibit adhesion molecules within biofilms. Phytochemicals have demonstrated activity against QS pathways and efflux pumps. Metal ion chelators like deferiprone interfere with iron acquisition, which is essential for biofilm stability. Nanoparticles (NPs), ranging from metallic and polymeric to lipid-based and cyclodextrin-based systems, enhance drug delivery and biofilm penetration. CRISPR-Cas systems provide precise genome editing to target resistance genes and virulence factors. Rhamnolipids disrupt biofilm matrix integrity, while enzymes such as dispersin B degrade extracellular polymeric substances. Photodynamic and laser therapies offer localized disruption of biofilm structures through oxidative stress. Collectively, this review offers a transformative complementary approach to traditional antibiotics, enhancing treatment efficacy while potentially reducing the emergence of resistance. Continued research on delivery systems, safety profiles, and synergistic combinations will be pivotal for their clinical translation against S. aureus infections.
    Keywords:  MRSA; antibiofilm approaches; antimicrobial resistance; biofilm formation; quorum sensing
    DOI:  https://doi.org/10.1556/1886.2025.00050
  23. ACS Infect Dis. 2025 Oct 24.
      Tuberculosis (TB) remains the world's deadliest bacterial infection, with 8.2 million newly notified cases and an estimated 1.25 million deaths in 2023. Alarmingly, ∼19% of multidrug- or rifampicin-resistant (MDR/RR) strains already meet the World Health Organization (WHO) definition of pre-XDR-TB because they are resistant to at least one fluoroquinolone (FQ). Although gyrA/gyrB target-site mutations dominate clinical FQ resistance, Mycobacteria also rely on transcriptional networks that help them withstand the oxidative and DNA strand-breaking stress caused by these drugs. Central to this response is the heterodimeric transcription factor pafBC, whose WYL domain binds to single-stranded DNA and redirects RNA polymerase to a dedicated promoter set, thereby orchestrating a LexA-independent DNA-damage response (DDR). Up-regulation of pafBC has been linked to enhanced intracellular survival of M. tuberculosis and nontuberculous mycobacteria after FQ exposure, yet the downstream phenotypes and their connection to drug or phage resistance have remained unclear. Here, we demonstrate that deletion of pafBC in Mycobacterium smegmatis profoundly remodels the cell envelope, as evidenced by altered colony rugosity, reduced sliding motility, enhanced aggregation, and a three- to 5-fold decline in quantitative biofilm biomass. Untargeted lipid profiling revealed the selective depletion of long-chain trehalose polyphosphates and other apolar glycolipids that normally decorate the outer membrane─lipid classes that have recently been shown in other studies to serve as essential receptors for therapeutic mycobacteriophages such as BPs and Muddy. Consistent with this lipid deficit, the pafBC mutant exhibited markedly reduced phage adsorption and plaque formation; ectopic expression of RecA restored adsorption efficiency, implicating DDR envelope crosstalk in antiphage defense. Complementation with wild-type pafBC rescued lipid composition, biofilm mass, and phage resistance, whereas a WYL-domain mutant that cannot bind single-stranded DNA failed to do so, underscoring the necessity of canonical pafBC activation for envelope homeostasis. Immunoprofiling in THP-1 macrophages further showed that pafBC-proficient bacilli induce significantly higher secretion of IL-1β, TNF-α, and IL-6 compared to their isogenic mutant. This effect correlated with the presence of intact surface glycolipids, molecules known to interact with scavenger and Toll-like receptors on phagocytes and to enhance opsonizing antibody deposition at the host-pathogen interface. Overall, our findings connect the molecular mechanisms of the pafBC DDR with observable phenotypes such as fluoroquinolone tolerance, biofilm structure, phage resistance, and host immune recognition, by highlighting cell-envelope remodeling as the central factor.
    Keywords:  DNA-damage response; biofilm architecture; cell-envelope remodeling; fluoroquinolone resistance; mycobacteriophage adsorption; pafBC
    DOI:  https://doi.org/10.1021/acsinfecdis.5c00627
  24. PLoS Biol. 2025 Oct;23(10): e3003042
      Retrons are bacterial immune systems that protect a bacterial population against phages by killing infected hosts. Retrons typically comprise a reverse transcriptase (RT), a template noncoding RNA that is partially reverse transcribed into RT-DNA, and a toxic effector. The reverse transcriptase (RT), noncoding RNA, and RT-DNA complex sequester the toxic effector until triggered by phage infection, at which point the toxin is released to induce cell death. Due to their ability to produce single-stranded DNA in vivo, retrons have also been engineered to produce donor templates for genome editing in both prokaryotes and eukaryotes. However, the current repertoire of experimentally characterized retrons is limited, with most retrons sourced from clinical and laboratory strains of bacteria. To better understand retron biology and natural diversity, and to expand the current toolbox of retron-based genome editors, we developed a pipeline to isolate retrons and their bacterial hosts from a variety of environmental samples. Here, we identify seven new retron systems, each isolated from a different host bacterium. We characterize DNA production by these retrons and test their ability to defend against a panel of Escherichia coli phages. We find that two of these retrons are disrupted by other elements, in one case a group II intron and in another a separate defense system, yet both retrons still produce RT-DNA. For two other retrons, we further unravel their mechanism of defense by identifying the phage genes responsible for triggering abortive infection. Finally, we engineer these retrons for genome editing in E. coli, demonstrating their potential use in a biotechnological application.
    DOI:  https://doi.org/10.1371/journal.pbio.3003042
  25. Eur J Clin Microbiol Infect Dis. 2025 Oct 23.
       PURPOSE: Effective decolonization strategies for intestinal carriers of carbapenem-resistant Enterobacterales are essential to prevent severe life-threatening infections. In this work, we established gut colonization in Zophobas morio larvae (ZmL) using an OXA-48-producing Salmonella enterica ST198 strain (Sk-1) and assessed the commercial INTESTI bacteriophage cocktail (INTESTIbc) for decolonization.
    METHODS: ZmL were fed with food contaminated with Sk-1 (INTESTIbc-susceptible) for 3 days and then maintained on a non-contaminated diet until day 14 (T14). At T3, ZmL were grouped in untreated, dPBS- or INTESTIbc-treated (oral force-feeding on T3 and T5). At specified intervals, ZmL were sampled for quantification and characterization of Sk-1 (antibiotic/INTESTIbc susceptibility and whole-genome sequencing). ZmL microbiota was also investigated by 16S rRNA amplicon sequencing.
    RESULTS: ZmL were rapidly colonized by Sk-1 across all groups (T3: 4.3 × 106 CFU/mL). Untreated and dPBS-treated larvae remained consistently colonized (T10: 3.4-9.1 × 104 CFU/mL; T14: 2.9-5.9 × 104 CFU/mL), whereas INTESTIbc treatment induced a significant Sk-1 regrowth (T10: 4.0 × 106 CFU/mL; P < 0.05 vs. controls). Sk-1 strains recovered under different conditions between T7 and T14 did not show phenotypic and genotypic changes. Bacteriophages administration resulted in reduced relative abundance of potential bacterial competitors of Sk-1 (i.e., Pseudocitrobacter).
    CONCLUSIONS: ZmL can be used as a new in vivo model of intestinal colonization with S. enterica. However, INTESTIbc administration failed to achieve decolonization and instead promoted hazardous overgrowth of the inoculated pathogen. These findings highlight the need for further investigations to clarify the therapeutic potential or possible risks of broad-spectrum bacteriophage cocktails against intestinal infections/colonization caused by hyperepidemic S. enterica clones.
    Keywords:   Salmonella ; Zophobas ; Bacteriophages; Carbapenemase; Gut; Microbiota
    DOI:  https://doi.org/10.1007/s10096-025-05275-6
  26. Microb Pathog. 2025 Oct 21. pii: S0882-4010(25)00849-6. [Epub ahead of print]209 108124
      Multi-drug resistant (MDR) Escherichia coli has become one of the significant global health concerns, and this demands the development of alternative strategies for antimicrobials. The present study describes the isolation and characterisation of bacteriophage vB_Ec_DUEC01- a virulent member of the class Caudoviricetes-which could serve as a potential biocontrol agent against MDR E. coli. Electron microscopy showed an icosahedral capsid and a long, non-contractile tail. The one-step growth curve resulted in a latent period of 20 min with a high burst size of 97 PFU per infected cell. Moreover, the phage showed reasonable stability over a pH range of 3.0-12.0 and at moderate temperatures of 20 °C-40 °C. Whole-genome sequencing revealed a genome of 43,949 bp encoding 77 open-reading frames (ORFs), encoding structural, packaging, DNA replication and metabolism, and lysis proteins. No lysogeny-related, antibiotic resistance, or virulence factor genes were found. Phylogenetic analysis placed the phage in the Kagunavirus genus, with closely related therapeutically relevant phages. Results suggest that vB_Ec_DUEC01 is effective, genetically safe, and stable; therefore, it is a preliminary good candidate for application as a biocontrol agent against MDR E. coli. Further, host-range and in vivo efficacy studies are necessary to develop this application in antimicrobial therapy.
    Keywords:  Escherichia coli; Illumina sequencing; Kagunavirus; Lytic cycle; Multi-drug resistance; Phage therapy; Virulent phage
    DOI:  https://doi.org/10.1016/j.micpath.2025.108124