bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2025–07–13
nineteen papers selected by
Luca Bolliger, lxBio



  1. Eur J Med Res. 2025 Jul 09. 30(1): 605
       BACKGROUND: Antibiotic-resistant bacteria pose an urgent health threat as mutations have led to resistant strains that evade treatment. These bacteria form biofilms, complicating infection management. Bacteriophages are being recognized for their potential in phage therapy due to their effectiveness in rapidly targeting and eliminating bacterial hosts.
    MATERIALS AND METHODS: This systematic review examined the effectiveness of bacteriophages against biofilms created by antibiotic- and drug-resistant staphylococcal strains. A thorough search of the Embase, Web of Science, PubMed, and Scopus databases was conducted for studies published from 2012 to October 29, 2024, focusing on relevant research while excluding irrelevant studies.
    RESULTS: This systematic review assesses the effectiveness of phage-derived enzymes, including endolysins and depolymerases, as well as whole bacteriophages, in degrading biofilms and clearing bacteria. It also highlights how combining phages with antibiotics or other agents can improve biofilm removal. The review explores the potential applications of phage therapy in various contexts, such as infections related to milk, silicone surfaces, synovial fluid, and prosthetic joint materials. Overall, while phage therapy shows promise as an alternative to antibiotics, additional research is necessary to refine treatment methods and ensure safety.
    CONCLUSIONS: Bacteriophages hold potential as a standalone treatment and a complementary option to traditional antibiotics for managing S. aureus biofilms, but further research is needed to understand their clinical potential. Additional studies on phage selection, dosing, and administration methods are necessary, along with exploration of phage-antibiotic synergy mechanisms and assessment of the safety and environmental impacts of phage therapy.
    Keywords:   Staphylococcus aureus ; Antibiotic–bacteriophage combination; Antimicrobial resistance; Bacteriophage; Biofilms; Lysins; Synergism
    DOI:  https://doi.org/10.1186/s40001-025-02781-3
  2. Mol Biotechnol. 2025 Jul 09.
      Bacteriophages, viruses that specifically target and lyse bacterial cells, were first discovered over a century ago. At present, as drug-resistant bacterial infections and cancer pose some of the greatest challenges to global health, phage therapy has emerged as a potential solution to both issues. This review focuses on the three critical steps involved in the development of phage therapy: phage isolation, host characterization, and assessment of therapeutic efficacy in both in vitro and in vivo models. The therapeutic potential of phage therapy is discussed across a range of infections, including pulmonary, gastrointestinal, dermal, and dental diseases, along with its application in treating various cancers, such as melanoma, glioblastoma, breast cancer, and colon cancer. Furthermore, this review highlights the distinct advantages of phage therapy over traditional treatments, as well as the challenges and limitations hindering its widespread adoption. Future prospects, including the need for personalized phage therapy and overcoming regulatory and safety hurdles, are also considered.
    Keywords:  Bacterial infections; Bacteriophage; Cancer; Phage therapy
    DOI:  https://doi.org/10.1007/s12033-025-01466-w
  3. Infection. 2025 Jul 07.
      Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a major challenge in clinical settings due to high morbidity, mortality, and limited treatment options. In response, phage therapy has reemerged as a promising alternative to conventional antibiotics. In this study, two lytic bacteriophages, Kpn_PImp2 and Kpn_PImp3, were isolated from urban sewage, a rich source of phages owing to its diverse microbial community. These phages demonstrated remarkable pH stability and thermostability, ensuring their activity under a variety of environmental and physiological conditions. Genomic analysis suggests that both phages likely belong to the Webervirus genus within the Caudoviricetes class, characterized by tailed phages with double-stranded DNA. Importantly, neither phage harbors lysogenic, toxin, nor antimicrobial resistance genes, affirming their safety for therapeutic applications. Comparative studies of tail fiber proteins, which play a crucial role in host specificity, indicate that structural variations may account for the distinct host ranges of Kpn_PImp2 and Kpn_PImp3. Moreover, both phages exhibited the ability to inhibit and disrupt biofilm formation, a key factor in CRKP persistence and resistance. Their biofilm-disrupting properties could potentially enhance the penetration and efficacy of antibiotics in combination therapies. The in vivo efficacy of these phages was further validated using the Galleria mellonella infection model, where treatment led to a significant reduction in larval mortality. However, a cocktail combining both phages did not show synergistic benefits over monophage therapy, likely due to shared host-cell receptors. These findings highlight Kpn_PImp2 and Kpn_PImp3 as promising candidates for phage therapy against CRKP, warranting further research into resistance mechanisms, delivery methods, and combination therapies to fully realize their therapeutic potential. This study also expands the bacteriophage resources against K. pneumoniae and provides valuable insights for phage-based treatments.
    Keywords:   Klebsiella pneumoniae ; Bacteriophage; Biofilm; Carbapenem-resistant; Phage therapy
    DOI:  https://doi.org/10.1007/s15010-025-02599-5
  4. Microb Pathog. 2025 Jul 03. pii: S0882-4010(25)00593-5. [Epub ahead of print]207 107868
      In recent years, multidrug-resistant Rhodococcus equi has emerged globally. Phage therapy has been attracting renewed attention as an alternative to antibiotics. In this study, we aimed to isolate and maintain R. equi bacteriophages and characterize them as a potential agent for phage therapy to treat R. equi infection. Phages with lytic activity, ReT1, were induced with mitomycin C from R. equi Kuma83-10 strain that genomic analysis revealed to possess phage-like sequences. ReT1 showed two plaque types immediately after induction, and the cloned ones were designated ReT1v-1 and ReT1v-2. These phages could be maintained in the laboratory without titer reduction, were morphologically Siphoviridae-like phages, and were stable under the environmental conditions expected for use as phage therapy. ReT1v-2 was altered into a lytic phage lacking the region around the integrase gene from the ReT1v-1 genome. Both phages did not differ in their host range (narrow range), that is, formed spots only in R. equi JID03-27, of the 18 strains examined. However, ReT1v-2 showed the most pronounced bactericidal effect against JID03-27:pVAPA strains, which infected cultured macrophages. This result was consistent in vivo, with the ReT1v-2-treated group showing growth inhibition in mice. The collection of more phages with lysogenic activity against R. equi and with different characteristics will lead to more options for phage cocktail formulations in anticipation of resistance. The results of this study support the possibility of developing formulations based on these phages.
    Keywords:  Bacteriophage; Macrophage; Rhodococcus equi; Whole genome sequence
    DOI:  https://doi.org/10.1016/j.micpath.2025.107868
  5. Front Microbiol. 2025 ;16 1606351
       Background: Acinetobacter baumannii is a common hospital pathogen that poses a serious clinical challenge due to its rapidly increasing resistance to antibiotics. Phage therapy has been successfully used to treat antibiotic resistant A. baumannii infections. The aim of this study was to comprehensively assess the current status and trend of research on the application of phages in A. baumannii infections through bibliometric analysis.
    Methods: Studies on phages and A. baumannii infections were searched in the Web of Science Core Collection database and relevant articles were selected for inclusion in the study based on the inclusion criteria. Bibliometric and visual analysis of the included publications were performed using VOSviewer and CiteSpace software.
    Results: A total of 264 studies were included. There is an increasing trend in the number of publications per year from 2010 to 2024. China was the leading country with 35.98% of the total publications. Tzu Chi University and Lin, Nien-Tsung were the most influential institution and author, respectively. The journal with the highest H-index was Frontiers in Microbiology, and Viruses-Basel was the most prolific journal. Antimicrobial Agents and Chemotherapy was the most cited journal. Phages endolysin and phage therapy were found to be the widely researched aspects, biofilm, phage resistance and synergistic effect are recent research hotspots.
    Conclusion: In the last decade or so, this is the first bibliometric study that systematically describes the research hotspots and development trends on phages in A. baumannii infections. Research hotspots should be given more attention.
    Keywords:  Acinetobacter baumannii; bibliometric analysis; biofilm; phage resistance; phages therapy; synergistic effect
    DOI:  https://doi.org/10.3389/fmicb.2025.1606351
  6. J Infect Chemother. 2025 Jul 08. pii: S1341-321X(25)00167-9. [Epub ahead of print] 102770
       INTRODUCTION: Personalized phage therapy is used in Europe and the United States to treat intractable infections caused by drug-resistant bacteria. This pilot study aimed to acquire feasibility data for clinical trials of individualized phage therapy in Japan.
    METHODS: An observational study was conducted from August 2023 to September 2024 in adults with drug-resistant bacterial infections and treatment failure or recurrence/relapse following antimicrobial therapy. Phages with activity against the detected bacteria were then identified from the environment and an existing phage library.
    RESULTS: Thirty patients with drug-resistant bacterial infections were enrolled. Of these, six (20%) died within 30 days of detection. The most commonly detected bacteria were methicillin-resistant Staphylococcus aureus (MRSA) (n=10, 33.3%) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) (n=5, 16.7%). The most common nontuberculous mycobacterium (NTM) was Mycobacterium avium (n=4, 13.3%), followed by Mycobacterium abscessus (n=2, 6.7%). In terms of infection types, respiratory tract infections were the most common (n=13, 43.3%), followed by bone and joint infections (n=6, 20%) and skin and soft tissue infections (n=6, 20%). Phages with a titer of 108 PFU/ml or higher could be prepared for 26 out of 30 strains (86.7%). Phages against CRPA were more readily identified from the environment than for MRSA and NTM. A phage against CRPA was purified to a lipopolysaccharide concentration of 0.023 EU/108 PFU.
    CONCLUSION: Personalized phages can be prepared for intractable infections caused by drug-resistant bacteria. These results support clinical trials to implement personalized phage therapy in Japan.
    Keywords:  CRPA; Japan; MRSA; drug-resistant bacteria; phage
    DOI:  https://doi.org/10.1016/j.jiac.2025.102770
  7. Health Sci Rep. 2025 Jul;8(7): e70956
       Background and Aim: It is now known that bacteria are highly interactive and exhibit a range of complex cooperative behaviors, including conjugal plasmid transfer, toxins, swarming, drug resistance, toxin production, biofilm development, and other virulence traits. The development of phage-antibiotic synergy (PAS) could be a useful weapon against bacterial infections where antibiotics increase phage replication and antimicrobial activity. This study investigates the therapeutic potential of PAS in combating bacterial infections, focusing on the mechanisms and clinical implications.
    Methods: A comprehensive review of recent literature was conducted analyzing studies on PAS, including their effects on biofilm degradation, multidrug-resistant (MDR) bacteria, and toxin-producing pathogens. Key factors such as timing, dosing and compatibility of phage-antibiotic combinations were examined.
    Results: PAS showed promising results in various bacterial infections. The combination of phages and antibiotics restored the susceptibility of MDR strains, facilitated the degradation of biofilms and minimized the need for high doses of antibiotics, thereby reducing potential side effects. However, challenges such as the emergence of resistance and antagonistic interactions with certain combinations remain. Key factors influencing the efficacy of PAS include phage and antibiotic dosing, timing of administration, and the physiological state of the bacteria.
    Conclusion: PAS has potential applications in the treatment of complex infections. Despite the promising results, further research is essential to standardize protocols, optimize therapeutic combinations and address safety concerns. Clinical trials focusing on phage selection, resistance management and patient-specific treatments will be crucial for the translation of PAS into clinical practice.
    Keywords:  MDR; antibiotic; antimicrobial resistance; bacteriophage; biofilms; phage–antibiotic synergy
    DOI:  https://doi.org/10.1002/hsr2.70956
  8. Sci Adv. 2025 Jul 11. 11(28): eadx4183
      Ocular infections pose notable blindness risks. Despite its advantages in inhibiting multidrug-resistant bacteria and eliminating biofilms, phage therapy suffers low phage vitality, limited ocular retention, and lack of anti-inflammatory abilities toward ocular infections. Here, wearing phages individually with an adhesive drug-loadable nanohelmet is reported to advance phage therapy. The nanohelmet is formed by depositing arginine-glycine-aspartic acid-modified chitosan on negatively charged phage head through electrostatic interactions, followed by codepositing anti-inflammatory agents via physical adsorption. Nanohelmet formation shows a negligible influence on phage vitality and is applicable to helmet diverse phages. Because of the cationic nature and the presence of arginine-glycine-aspartic acid sequence, such nanohelmet exhibits a double-lock adhesion fashion to ocular surface, prolonging phage retention after instillation. Together with sustained drug release, helmeted phages potently inhibit bacteria, eliminate biofilms, and effectively suppress localized inflammation. In mice with multidrug-resistant pathogen-induced keratitis, helmeted phages achieve superior therapeutic efficacies, even compared to clinical therapeutics.
    DOI:  https://doi.org/10.1126/sciadv.adx4183
  9. Biomater Adv. 2025 Jul 04. pii: S2772-9508(25)00230-4. [Epub ahead of print]177 214403
      First-line treatments for treating wound infections are under threat from the increase in antimicrobial resistant bacteria, a threat further exacerbated in burn wounds in which the immune response to the infection site is blocked by burned skin. Herein, we report a tuneable and in situ-gelling poly(oligoethylene glycol methacrylate) bulk hydrogel containing bacteriophage (phage), viruses that allow for highly efficient and specific killing of bacteria without the need for conventional antibiotics. The resulting phage-hydrogel has suitable mechanical strength (1.5 kPa compressive modulus) and stability (up to 5 days when fully hydrated) for use as a burn wound dressing while also maintaining excellent antibiotic properties (>4-log reduction of Pseudomonas aeruginosa in a murine in vivo infection burn wound model). Coupled with the beneficial hydrating properties of hydrogels for promoting burn wound healing, the phage-hydrogel dressing offers potential for managing complex burn wound infections.
    Keywords:  Bacteriophage; Burn wound; Hydrogel; Infection
    DOI:  https://doi.org/10.1016/j.bioadv.2025.214403
  10. Microb Pathog. 2025 Jul 08. pii: S0882-4010(25)00611-4. [Epub ahead of print]207 107886
      This study was designed to evaluate the phenotypic properties of PBST35-resistant Salmonella enterica subsp. enterica serovar Typhimurium in association with adaptive trade-offs between bacteriophage resistance and antibiotic resistance. Bacteriophage-insensitive S. enterica Typhimurium (BIST) variants were isolated and analyzed using the spot test, adsorption assay, and biofilm formation assay. The effects of bacteriophage and antibiotic combinations were evaluated using the disk diffusion assay, antibiotic susceptibility assay, and checkerboard assay to evaluate synergy. PBST35 bacteriophage showed a latent period of 10 min, a burst period of 50 min, and a burst size of 72 PFU/CFU. The swimming motility of BIST decreased significantly to 4 %, compared to 70 % in bacteriophage-sensitive S. enterica Typhimurium (BSST). BIST showed increased susceptibility to cefotaxime (CTX), ceftriaxone (CRO), meropenem (MEM), ciprofloxacin (CIP), levofloxacin (LEV), kanamycin (KAN), chloramphenicol (CHL), and sulfamethoxazole/trimethoprim (SXT). The MIC values of CTX, CIP, gentamicin (GEN), and polymyxin B (PMB) against BIST decreased by 2-fold, 1-fold, 2-fold, and 2-fold, respectively. The fractional inhibitory concentration (FIC) indices for BIST were 0.5 for CTX, 1.0 for CIP, 0.5 for GEN, and 0.5 for PMB. The sequential treatment of GEN and PBST35 reduced BSST biofilms by 87 % and BIST biofilms by 68 %. This study provides the potential of combining bacteriophages with antibiotics as a promising strategy to overcome resistance in bacteriophage-resistant strains and supports the development of integrated antimicrobial approaches to combat the growing threat of multidrug-resistant bacterial infections.
    Keywords:  Adaptive trade-offs; Bacteriophage resistance; Bacteriophage-antibiotic synergy; Biofilms; Drug resistance; Sequential antibiotic treatment
    DOI:  https://doi.org/10.1016/j.micpath.2025.107886
  11. bioRxiv. 2025 Jul 02. pii: 2025.07.02.662641. [Epub ahead of print]
      Bacteria have evolved sophisticated antiphage systems that halt phage replication upon detecting specific phage triggers. Identifying phage triggers is crucial to our understanding of immune signaling, however, they are challenging to predict. Here we used an expansive plasmid library that expressed 400 phage protein-coding genes from 6 different phages to identify novel triggers of known and undiscovered antiphage systems. We transformed our library into 72 diverse strains of E. coli . Each strain natively harbors a different suite of antiphage systems whose activation typically inhibits growth. By tracking plasmids that were selectively depleted, we identified over 100 candidate phage trigger- E. coli pairs. Two phage trigger proteins were investigated in detail, revealing a novel antiphage system that detects multiple phage tail fiber proteins and identifying major capsid protein as the activating ligand of the antiphage system Avs8. These experiments provide a unique dataset for continued definition of the molecular details of the bacterial immune system.
    DOI:  https://doi.org/10.1101/2025.07.02.662641
  12. Expert Opin Investig Drugs. 2025 Jul 09.
       INTRODUCTION: Multidrug-resistant Pseudomonas aeruginosa infections have disseminated globally and are associated with high mortality due to the considerable virulence of the pathogen and the limited therapeutic options. This has led to efforts to develop new treatment options for such infections.
    AREAS COVERED: This review evaluated the most recent literature on the relevant traditional and non-traditional antibiotics currently being developed in Phases 1, 2, and 3 clinical trials. We conducted a PubMed literature search, as well as a backward citation search of relevant studies. Traditional agents in clinical development include β-lactam/β-lactamase inhibitors (funobactam, taniborbactam, QPX2014-xeruborbactam), aminoglycosides (apramycin), polymyxin derivatives (upleganan, MRX-8, and SPR741), fluoroquinolones (MP-376), and lipopolysaccharide transport inhibitors (murepavadin). Non-traditional antibiotics in clinical development include anti-virulence agents (fluorothiazinone), monoclonal antibodies (INFEX-702, TRL-1068, and CMTX-101), bacteriophages (AP-PA02, YPT-01, BX004-A, and WRAIR-PAM-CF1), and miscellaneous agents (AR-501, PLG-0206, SNSP-113, OligoG CF-5/20, and ALX-009).
    EXPERT OPINION: A considerable number of antimicrobial agents, some with novel mechanisms of action, are in clinical phases of development for treating Pseudomonas aeruginosa infections. The urgent need for more therapeutic options necessitates the rapid optimization of progress to introduce new agents into clinical practice.
    Keywords:  Clinical trial; non-traditional antibiotic; pseudomonas aeruginosa; traditional antibiotic
    DOI:  https://doi.org/10.1080/13543784.2025.2532443
  13. Adv Healthc Mater. 2025 Jul 08. e2500875
      Bacterial resistance poses a serious clinical challenge. This study designs a peptide-enhanced bioactive hydrogel with a photodynamic-phage synergistic antibacterial effect that is an efficient antibacterial and promotes wound healing. LaFeO3@C3N4 is characterized with XRD, XPS, SEM, and UV-vis, and the photodynamic properties of LaFeO3@C3N4 producing ROS are confirmed by EPR. The peptide QHREDGS-modified boronate ester hydrogel is characterized by FT-IR, 1HNMR, SEM, dynamic mechanical analysis, etc. Combined LaFeO3@C3N4 and phage phipa10, the peptide QHREDGS-modified boronate ester hydrogel shows synergistic antibacterial and wound healing effects in both in vitro and in vivo experiments. Moreover, the molecular mechanism of tissue regeneration is explored by transcriptomic and protein expression analysis, and the results show that the peptide-enhanced bioactive hydrogel combined with photodynamic-phage synergistic antibacterial therapy system (QBC@DP-P-phi) significantly promoted cell proliferation and migration by regulating key signaling pathways such as PI3K-Akt, VEGF, and MAPK. Overall, this novel hydrogel is promising for the clinical treatment of infected wounds.
    Keywords:  antibacterial strategy; bioactive hydrogel; infected wounds; phage therapy; photodynamic therapy
    DOI:  https://doi.org/10.1002/adhm.202500875
  14. Rev Cardiovasc Med. 2025 Jun;26(6): 36386
      This study reviews the correlation between the gut virome and cardiovascular diseases (CVDs) and investigates the potential role of the gut virome in CVD progression. The gut virome, which includes bacteriophages and eukaryotic viruses, interacts with the intestinal microbiota and the host immune system, and affects the overall health of the host. Previous studies have demonstrated that alterations in the gut virome are closely associated with various cardiovascular conditions, including hypertension, atherosclerosis, atrial fibrillation, heart failure, and viral myocarditis. Thus, the gut virome may contribute to CVD development by regulating intestinal microecology and immune responses, affecting intestinal barrier function and systemic inflammatory responses. However, despite advancements in gut virome research, our understanding of the specific mechanisms involved and therapeutic potential in CVDs remains limited. Future developments in virus databases and advancements in sequencing technology are expected to offer new insights and methods for the early diagnosis and accurate treatment of CVDs.
    Keywords:  bacteriophage; cardiovascular disease; gut microbiota dysbiosis; gut virome
    DOI:  https://doi.org/10.31083/RCM36386
  15. J Wound Care. 2025 Jul 02. 34(7): 506-512
      Due to its inactivating effect on bacteria, cold atmospheric plasma (CAP) has been shown to be successful in the treatment of hard-to-heal (chronic) and infected wounds. In this case series, 15 patients with a total of 20 wounds were treated with a mobile CAP device and the bacterial load of the wound simultaneously observed using a MolecuLight i:X (MolecuLight Inc., US) camera. In 60% of cases, the bacterial load could be brought under control despite minimal CAP application. This procedure offers the advantage of being able to directly visualise wound bacterial load and, therefore, the inactivation of bacteria is also directly visible. The use of the two devices complemented each other; supporting wound management and analysis of its effectiveness.
    Keywords:  bacterial load; chronic wound; cold atmospheric plasma; hard-to-heal; infected wound; non-invasive physical plasma; wound; wound bed preparation; wound care; wound dressing; wound healing
    DOI:  https://doi.org/10.12968/jowc.2025.0132
  16. Br J Community Nurs. 2025 Jul 01. 30(Sup7): S14-S18
      Artificial intelligence (AI) has revolutionised the world and it is increasingly being used in healthcare settings. Wound care is one such area where the use of AI can be a game changer. From checking in on patients to monitoring the condition of wounds, AI can help community nurses with their workload and allow them to dedicate their time to where it is most needed. This interview features insights from Karen O'Rourke, lead wound care nurse at Home Wound Care. Her team has been part of the pilot AI technology clinic incorporating a variety of AI tools in the treatment of chronic and hard-to-heal wounds.
    Keywords:  artificial intelligence; community wound care; comorbidities; hard-to-heal wounds; patient outcomes
    DOI:  https://doi.org/10.12968/bjcn.2025.0093
  17. Smart Mol. 2024 Mar;2(1): e20230021
      This comprehensive review delves into a unique intersection of hydrogels as smart molecules and their transformative applications in ophthalmology. Beginning with the foundational definition, properties, and classification of hydrogels, the review explores their synthesis and responsive capabilities. Specific applications examined encompass topical drug delivery, contact lenses, intravitreal drug delivery, ocular adhesives, vitreous substitutes, and cell-based therapy. A methodical analysis, including an overview of relevant ocular structures and a comparative evaluation of hydrogel-based solutions against traditional treatments, is conducted. Additionally, potential constraints, translation challenges, knowledge gaps, and research areas are identified. Our methodical approach, guided by an extensive literature review from 2017 to 2023, illuminates the unprecedented opportunities offered by hydrogels, along with pinpointing areas for further inquiry to facilitate their transition into clinical practice.
    Keywords:  ocular diseases; ocular treatments; smart hydrogels
    DOI:  https://doi.org/10.1002/smo.20230021
  18. J Mycol Med. 2025 Jul 03. pii: S1156-5233(25)00033-2. [Epub ahead of print]35(3): 101570
      Lung abscess is a severe but rare complication among non-transplanted cystic fibrosis (CF) patients. <10 cases have been reported in the international literature so far and bacteria were considered the responsible pathogen. We present two cases of CF adolescent patients who developed lung abscess from A. fumigatus, critically revealed with chest Computed Tomography. In one patient, a thyroid abscess was additionally detected. Both patients presented with fever, not responding to antibiotic therapy. Microbial cultures and molecular testing aided detection of the pathogen. Both patients responded well to antifungal treatment.
    Keywords:  Aspergillus fumigatus; Cystic fibrosis; Lung abscess; Thyroid abscess
    DOI:  https://doi.org/10.1016/j.mycmed.2025.101570