bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2025–10–12
eighteen papers selected by
Luca Bolliger, lxBio



  1. Int J Antimicrob Agents. 2025 Oct 08. pii: S0924-8579(25)00195-5. [Epub ahead of print] 107640
      The global escalation of antimicrobial resistance (AMR) has intensified the search for alternative therapies, with bacteriophage (phage) therapy re-emerging as a promising solution. This review critically examines the therapeutic potential of phage therapy against multidrug-resistant (MDR) ESKAPE pathogens which are among the leading causes of hospital-acquired infections. The review discusses the distinct antibacterial strategies of phage namely, targeted lysis, enzymatic biofilm disruption, and synergy with antibiotics. It also explores the molecular regulation of phage life cycles, highlighting the therapeutic importance of the lytic-lysogenic switch. A central focus is the interplay between advanced delivery systems such as liposomes, hydrogels, nanofibers, and nanoemulsions, and specific administration routes including oral, topical, intravenous, intranasal, and intravesical approaches. These delivery strategies are essential for overcoming key physiological barriers such as gastric acidity, enzymatic degradation, and immune clearance, thereby enhancing phage stability, retention, and therapeutic efficacy. Recent innovations in phage engineering are also explored, particularly the use of CRISPR-Cas systems, synthetic biology, and continuous evolution platforms to broaden host range and optimize lytic function. The review further evaluates emerging clinical evidence, including outcomes from compassionate use cases and early-phase trials, which emphasize both the safety and therapeutic potential of phage therapy in real-world settings. Despite these advances, significant challenges persist, including bacterial resistance to phages, the need for regulatory clarity, and scalability of personalized treatments. With the integration of microbiology, nanotechnology, and clinical practice, phage therapy bridges the gap between ecological solutions and modern medicine, positioning itself as a versatile, sustainable pillar in the post-antibiotic era.
    Keywords:  Bacteriophage; Clinical trials; ESKAPE pathogens; Phage delivery; Phage therapy; and Routes of administration
    DOI:  https://doi.org/10.1016/j.ijantimicag.2025.107640
  2. Mol Biol Rep. 2025 Oct 09. 52(1): 997
      Bacteriophages, viruses that specifically infect bacteria, have emerged as a valuable tool in diagnostics due to their unique specificity and adaptability. This review explores the diverse applications of bacteriophages in diagnostic methods, from traditional phage typing to advanced molecular techniques such as phage display and PCR-based diagnostics. It highlights their use in identifying bacterial strains, monitoring fermentation processes, and diagnosing critical conditions like tuberculosis, MRSA infections, and cancer. Innovations such as phage-based biosensors and reporter phages enhance the speed and precision of diagnostics, offering significant advantages over traditional methods. Challenges, including bacterial resistance and immune responses to phages, are also discussed alongside strategies for mitigation, such as phage cocktails and engineering. Integrating phage technology with modern bioscience holds promise for addressing antibiotic resistance and revolutionizing clinical and industrial diagnostics. This comprehensive analysis underscores the potential of bacteriophages to transform the diagnostic landscape while identifying areas requiring further research and development.
    Keywords:  Antibiotic resistance; Bacteriophages; Molecular diagnostics; Phage therapy; Phage-based diagnostics
    DOI:  https://doi.org/10.1007/s11033-025-10967-5
  3. BMC Microbiol. 2025 Oct 10. 25(1): 649
       BACKGROUND: Shigella and Salmonella are major foodborne and waterborne pathogens responsible for acute gastrointestinal infections and significant global morbidity and mortality. Both species are capable of forming bacterial biofilms in the food processing industry, a key survival mechanism that significantly reduces the effectiveness of antibacterial drugs. The global rise in antimicrobial resistance (AMR) necessitates the urgent development of new strategies. Bacteriophages, particularly phage cocktails, provide a potential alternative because of their host specificity and ability to degrade biofilms.
    RESULTS: In this study, a new bacteriophage, Sspk23, infecting Shigella sonnei, was isolated from lake water and biologically characterized to assess its lytic activity and stability under varying conditions. Furthermore, this study investigates the effectiveness of a phage cocktail, including a newly isolated Sspk23 and two previously identified phages, Sfk20 and STWB21, against Shigella and Salmonella infections with a focus on its ability to combat single and polymicrobial infections. The biofilm removal potential of the phage cocktail was observed using Scanning Electron Microscopy (SEM) and Confocal Laser Scanning Microscopy (CLSM), and also quantitatively assessed in a microtiter plate. Cytotoxicity tests were conducted on human adherent epithelial cell line and macrophage cell line to confirm the safety of the phage and phage cocktail for therapeutic use.
    CONCLUSIONS: The findings demonstrate the possibility of a phage cocktail as a substitute for conventional antibiotics in controlling Shigella and Salmonella infections. Additionally, their capacity to destroy biofilms indicates potential applications in clinical therapies, environmental remediation, and food safety. Future studies will be focused on phage-antibiotic synergy optimization and in vivo validation to combat multidrug-resistant (MDR) bacteria.
    Keywords:   Salmonella ; Shigella ; Biofilm; Lytic bacteriophage; Phage cocktail
    DOI:  https://doi.org/10.1186/s12866-025-04328-2
  4. PLoS One. 2025 ;20(10): e0334139
      Pseudomonas aeruginosa, an opportunistic pathogen associated with wound infections, resists many commonly available antibiotics. Its ability to form biofilm provides an additional trait to evade antibiotics. Biofilm-associated infections are difficult to treat, raising the need for alternative strategies. Thus, this research aimed to investigate the potential of bacteriophage to disrupt the biofilm produced by P. aeruginosa isolated from wound infections. Wound samples were collected aseptically, processed for the isolation of P. aeruginosa, and identified by standard microbiological methods. Antimicrobial susceptibility was determined by the Kirby-Bauer disc diffusion method. Bacteriophages were isolated using the double-layer agar method. Phenotypic assessment of biofilm formation by the isolates and its reduction by phages was conducted by the tissue culture plate assay. Out of 647 wound samples processed, 96 P. aeruginosa were isolated. Piperacillin/tazobactam was the most effective antibiotic, while doxycycline was the least effective. Among the total isolates, 86 (89.6%) were multidrug-resistant (MDR) and 69 (71.9%) were biofilm producers. Three different phages isolated from sewage demonstrated a high specificity to P. aeruginosa. Of these, phage vB_PaeP_PS2 lysed the highest number of isolates (22.9%), including 17 MDR and 21 biofilm-producing isolates. The biofilm reduction assay demonstrated that phage treatment significantly reduced biofilm formation, with vB_PaeP_PS2 achieving a 58% reduction after 6 h of treatment. In conclusion, this study highlights the high prevalence of biofilm-producing MDR P. aeruginosa in wound infections and, for the first time in Nepal, demonstrates the potential of locally isolated phages to lyse biofilm-forming MDR isolates and disrupt their biofilms.
    DOI:  https://doi.org/10.1371/journal.pone.0334139
  5. Front Pharmacol. 2025 ;16 1656302
       Introduction: Chronic wounds are a significant source of patient morbidity, and ineffective treatment can lead to complications that are difficult and costly to manage. Given the limitations of current therapies, repurposing medications with well-studied safety and accessibility profiles offers a promising strategy for advancing wound care.
    Methods: A comprehensive review of the existing literature was conducted to evaluate the role of serotonin-modulating pharmacotherapy in wound healing.
    Results: Serotonergic signaling plays a multifaceted role in wound healing and evidence increasingly supports serotonin-modulating pharmacotherapy as having favorable angio-regulatory, immunomodulatory, and antimicrobial wound healing effects. Preclinical and clinical studies have demonstrated that topical administration of serotonin-modulating pharmacotherapy may improve wound healing outcomes.
    Discussion: findings of this study provide support for the use of serotonin-modulating pharmacotherapy, with a special focus on topical application, as an adjunctive treatment for chronic, non-healing wounds and highlight the need for further translational clinical investigation.
    Keywords:  chronic wounds; selective-serotonin reuptake inhibitor; serotonin; serotonin-modulating pharmacotherapy; wound healing
    DOI:  https://doi.org/10.3389/fphar.2025.1656302
  6. J Infect. 2025 Oct 06. pii: S0163-4453(25)00218-X. [Epub ahead of print]91(4): 106618
       INTRODUCTION: Metagenomic next-generation sequencing (mNGS) is an important tool for enhancing pathogen detection in infected patients. However, distinguishing between specimens that are infected or colonized is still a major challenge.
    OBJECTIVES: To explore the composition of bacteriophages in the blood and respiratory tract of the human body, the association between bacteriophage detection and bacterial infections, and whether bacteriophages can assist in differentiating infectious pathogens according to mNGS results.
    METHODS: Clinical samples from hospitalized patients were collected between January 2023 and February 2024. DNA and cell-free DNA were extracted from BALF and plasma retrospectively to identify the pathogens present, and bacteriophage annotations were conducted.
    RESULTS: A total of 299 samples, comprising 136 blood samples and 163 BALF samples, were obtained from 218 patients. Compared with the samples negative for bacteria, both blood and bronchoalveolar lavage fluid (BALF) samples infected with Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and S. aureus showed a corresponding increase in the proportions of phages related to these pathogens. In BALF samples with Acinetobacter baumannii infection, the proportions of Autographiviridae, Siphoviridae, and Myoviridae were significantly greater than those in the Acinetobacter baumannii colonization group. The sensitivity of Myoviridae for differentiating between infection and colonization was 86.36%, and the specificity was 52.94%.
    CONCLUSION: In sepsis, compared with conventional mNGS methods alone, the use of bacteriophages combined with mNGS was more effective in identifying causative pathogens and had higher specificity. These findings may provide new ideas and tools for improving clinical infection diagnosis.
    Keywords:  Acinetobacter baumannii; Bacteriophages; Colonization; Infection; Metagenomic next-generation sequencing; Myoviridae
    DOI:  https://doi.org/10.1016/j.jinf.2025.106618
  7. J Wound Care. 2025 Oct 02. 34(10): 874-880
       OBJECTIVE: Venous leg ulcers (VLUs) are hard-to-heal wounds primarily caused by venous insufficiency and venous hypertension. These wounds pose significant clinical and economic burdens, often failing to heal with standard compression therapy alone. Autologous whole blood clot (AWBC) therapy has emerged as a potential treatment for hard-to-heal wounds, complementing the body's natural wound healing mechanisms. This study aims to evaluate the outcomes of AWBC in a real-world setting for treating VLUs that have not responded to conventional therapies.
    METHOD: A multicentre observational registry study was conducted between August 2021 and December 2024 (NCT04699305) across multiple countries. Patients with hard-to-heal VLUs were included to receive AWBC application. Median wound duration at baseline was 13.5 months (interquartile range: 5.25, 36.0). AWBC applications were used alongside compression therapy, and outcomes were assessed in terms of percentage area reduction (PAR) and complete wound healing.
    RESULTS: There were 56 patients in the study cohort. AWBC treatment resulted in a mean wound area reduction of 71.3%. Complete healing was achieved in 45% of patients, while 54% exhibited a PAR >90%. Among the wounds treated, 44% that had persisted for >1 year achieved complete healing. Treatment duration varied, with some patients requiring extended therapy (12-20 weeks) to achieve significant wound progression. Adverse events were minimal and unrelated to treatment.
    CONCLUSION: In this study, AWBC therapy demonstrated high levels of effectiveness in treating hard-to-heal VLUs, particularly in patients whose wounds had failed to heal with standard compression therapy. AWBC therapy provides a supportive extracellular matrix, modulating inflammation and enhancing wound healing, demonstrating its valuable conjunction treatment to existing compression treatment protocols.
    Keywords:  autologous whole blood clot; extracellular matrix; hard-to-heal; treatment; venous hypertension; venous insufficiency; venous leg ulcers; wound; wound care; wound dressing; wound healing
    DOI:  https://doi.org/10.12968/jowc.2025.0419
  8. J Wound Care. 2025 Oct 02. 34(10): 790-796
      Forecasting indicates that the National Health Service in England may face a workforce shortage of up to 360,000 staff by 2036, reflecting challenges that resonate with wider international concerns. This means that wound care must evolve if it is to remain safe, effective and sustainable. One approach that could help is involving patients and carers more closely in their own wound care as evidence suggests that patients want to feel informed, involved and supported in playing a more active role in their wound care. When combined with the right dressing technology, shared wound care could release up to 3.5 billion hours of nursing time globally by 2030. Although many healthcare practitioners already support aspects of shared care, it has not yet become routine. This article sets out the foundations for how shared wound care can become routine practice. Incorporating evidence from key published studies, insights from a key opinion leaders-led 'Hackathon', and input from a patient focus group, work has been undertaken to shape what shared wound care could look like in real-world clinical practice. Practical ideas from the Hackathon included: a clinician checklist; a simplified wound care diary (with the option of a patient contract); visual explainers to show what shared wound care looks like in practice; and step-by-step guides for the care of different wound types. Feedback from the patient focus group showed that patients want to be empowered. With the right support and materials, such as wound diaries and change indicators, patients can often manage their wound care confidently and safely, positively improving their quality of life.
    Keywords:  nursing workforce; patient empowerment; quality of life; shared wound care; wound; wound care; wound dressing; wound healing; wound management framework
    DOI:  https://doi.org/10.12968/jowc.2025.0309
  9. Int J Biol Macromol. 2025 Oct 09. pii: S0141-8130(25)08685-4. [Epub ahead of print]330(Pt 3): 148128
      Peptide-loaded hydrogels have been extensively studied at present. Compared with traditional wound dressings such as gauze and bandages, they possess excellent biocompatibility, high drug-loading capacity, controlled drug release, and outstanding moisturizing properties. However, a comprehensive review focusing on peptide-based hydrogel bioadhesives for wound healing remains absent. This review explores the applications and mechanisms through which peptides and hydrogels facilitate wound healing. The use of peptide hydrogels has been shown to effectively enhance cell proliferation and migration, regulate inflammatory responses, accelerate collagen deposition and neovascularization, significantly shorten wound healing time, and improve healing outcomes. Peptides that promote wound healing include antimicrobial peptides, antioxidant peptides, antiviral peptides, and anticoagulant peptides, all of which contribute to enhancing the repair process and reducing the risk of infection. Furthermore, the hydrogel exhibits excellent physical stability and ease of use, presenting a promising new strategy for clinical wound management. Nevertheless, the application of hydrogels faces challenges such as inadequate mechanical properties and the need for further evaluation of biological safety. This study aims to establish a theoretical foundation for the application of multifunctional hydrogel scaffolds in promoting the wound healing process.
    Keywords:  Hydrogel; Polypeptide; Wound dressing; Wound healing
    DOI:  https://doi.org/10.1016/j.ijbiomac.2025.148128
  10. Nature. 2025 Oct 07.
      
    Keywords:  Antibiotics; Drug discovery; Infection
    DOI:  https://doi.org/10.1038/d41586-025-03218-x
  11. J Wound Care. 2025 Oct 02. 34(10): 768-777
       EXECUTIVE SUMMARY: This manuscript presents a unified and comprehensive policy framework addressing the flat-fee reimbursement model for skin substitutes, also referred to as cellular, acellular, and matrix-like products (CAMPs), proposed by the Centers for Medicare & Medicaid Services (CMS). These products are vital to treating hard-to-heal wounds, which disproportionately affect older patients, and those patients who are disabled and medically underserved. While CMS aims to curtail excessive spending and introduce payment consistency, the current proposal threatens access to life-saving therapies, endangers patient outcomes, and may destabilise clinical delivery infrastructures and manufacturing ecosystems critical to wound care.
    Keywords:  CAMPs; Local Coverage Determination; wound; wound care; wound dressing; wound healing
    DOI:  https://doi.org/10.12968/jowc.2025.0396
  12. Curr Stem Cell Rep. 2024 Jun;10(2): 30-36
       Purpose of review: Fetal therapy, a burgeoning field that encompasses prenatal surgical and medical interventions for congenital diseases, enables minimally invasive strategies of pharmacologic drug treatment before birth. We provide an overview of fetal drug delivery, its connections to current clinical practices, and key aspects for the clinician and researcher developing these approaches.
    Recent findings: A growing number of preclinical and clinical studies have demonstrated the success of nanomedicine for fetal applications, which we present here. In addition, we discuss the feasibility of fetal drug delivery from technical and ethical standpoints.
    Summary: Fetal drug delivery still has many areas that require further investigation to understand its full implications. This review provides insights into what is currently known about the feasibility of fetal drug delivery and highlights important ethical considerations as fetal drug delivery continues to improve and advance toward clinical translation.
    Keywords:  Fetal surgery; Fetal therapy; Nanomedicine; Nanotechnology
    DOI:  https://doi.org/10.1007/s40778-024-00235-w
  13. J Wound Care. 2025 Oct 02. 34(10): 778-780
      In the field of wound medicine and surgery significant attention is devoted to well-defined hard-to-heal (chronic) wounds, such as diabetic foot ulcers (DFUs), venous leg ulcers (VLUs) and pressure ulcers (PUs). These conditions dominate research, clinical guidelines and resource allocation, due to their clear aetiologies and high prevalence among specific patient populations. However, a substantial category of wounds-often labelled as 'other' open wounds under International Classification of Diseases (ICD)-10 codes-remain underappreciated and frequently excluded from analyses. These include non-specific open wounds without a particular aetiology, as well as surgical and trauma wounds that persist in outpatient settings without evolving into more specialised diagnoses. This opinion piece-building on the reimbursement framework proposed by Tettelbach et al.-argues that neglecting these 'other' wounds perpetuates inefficiencies in healthcare, exacerbates patient suffering and inflates economic burdens. By integrating comprehensive treatment strategies for all open wounds, regardless of aetiology, we can improve patient outcomes, reduce costs and advance equitable wound care interventions.
    DOI:  https://doi.org/10.12968/jowc.2025.0451
  14. J Pharm Anal. 2025 Sep;15(9): 101250
      Infectious keratitis (IK) is a leading cause of blindness worldwide, primarily resulting from improper contact lens use, trauma, and a compromised immune response. The pathogenic microorganisms responsible for IK include bacteria, fungi, viruses, and Acanthamoeba. This review examines standard therapeutic agents for treating IK, including broad-spectrum empiric antibiotics for bacterial keratitis (BK), antifungals such as voriconazole and natamycin for fungal infections, and antiviral nucleoside analogues for viral keratitis (VK). Additionally, this review discusses therapeutic agents, such as polyhexamethylene biguanide (PHMB), for the treatment of Acanthamoeba keratitis (AK). The review also addresses emerging drugs and the challenges associated with their clinical application, including anti-biofilm agents that combat drug resistance and nuclear factor kappa-B (NF-κB) pathway-targeted therapies to mitigate inflammation. Furthermore, methods of Photodynamic Antimicrobial Therapy (PDAT) are explored. This review underscores the importance of integrating novel and traditional therapies to tackle drug resistance and enhance drug delivery, with the goal of advancing treatment strategies for IK.
    Keywords:  Antibiotic resistance; Antimicrobial peptides; Emerging therapies; Infectious keratitis; Nanotechnology; Therapeutic drugs
    DOI:  https://doi.org/10.1016/j.jpha.2025.101250
  15. Cell Rep. 2025 Oct 08. pii: S2211-1247(25)01184-2. [Epub ahead of print]44(10): 116413
      Chronic obstructive pulmonary disease (COPD) severity correlates with airway microbial dysbiosis, yet bacteriophage roles remain unexplored. We characterized the lung DNA virome by re-analyzing 135 sputum metagenomes from 99 COPD patients and 36 healthy controls. We identified 1,308 viral operational taxonomic units, revealing progressively lower viral diversity correlating with disease severity. While viral and bacterial diversity typically showed strong positive correlations, patients with frequent exacerbations uniquely exhibited decoupled viral-bacterial relationships, indicating disrupted ecological dynamics. Comparing all COPD patients to controls, phages infecting anaerobic oral bacteria showed disproportionately lower abundance-Porphyromonas phages were 40-fold less abundant, despite only 4-fold lower bacterial abundance-while pathogen-associated phages showed no significant differences. We detected virulence factor-encoding phages, including two neuA-carrying Haemophilus phages in 7.4% of Haemophilus-colonized patients, associated with 82-fold higher bacterial abundance. These findings establish altered bacteriophage ecology as an unrecognized feature of COPD pathobiology, with differential phage-bacteria relationships that reshape lung microbial ecosystems, offering new perspectives for microbiome-targeted interventions.
    Keywords:  COPD; CP: Microbiology; bacteriophages; metagenomics; microbiome; respiratory; viromics
    DOI:  https://doi.org/10.1016/j.celrep.2025.116413
  16. J Wound Care. 2025 Oct 02. 34(10): 852-860
       OBJECTIVE: To examine the evidence for the clinical and cost-effectiveness of integrated digital wound management (IDWM) systems.
    METHOD: Using rapid review methodologies a search was conducted for studies evaluating IDWM systems in a healthcare setting. Searches were conducted in six research databases from 2012 up to 29 September 2023. A single reviewer screened all records. Data extraction was checked by a second reviewer.
    RESULTS: Searches identified 5100 articles for screening, of which 17 met the inclusion criteria. The findings from the included studies showed that IDWM reliably and accurately measured surface areas, particularly of wounds between 3-10cm2 in size; however, wound boundaries required manual adjustment for some wounds. Systems were not accurate for measuring wound depth. Feasibility studies (n=8) found IDWM is feasible, but there were limited comparative outcomes available. IDWM appeared to reduce the time taken to measure wounds in practice. The available evidence did not allow determination of cost-effectiveness.
    CONCLUSION: The results of this analysis showed that IDWM is a promising intervention for wound care; however, more comparative evidence is needed to determine whether it is clinically or cost-effective.
    Keywords:  chronic; clinical effectivness; cost-effectivness; hard-to-heal; integrated digital wound management systems; wound; wound care; wound dressing; wound healing; wound measurement
    DOI:  https://doi.org/10.12968/jowc.2024.0086
  17. Cancer Biother Radiopharm. 2025 Oct 06.
      Chemotherapy, radiation, and targeted biological treatments are examples of cancer therapies that have a significant effect on the immune system. They frequently interfere with the manufacture of immunoglobulins (Igs), which results in immunodeficiency. The processes via which these medications affect B cell activity and antibody production are examined in this review, with an emphasis on cytokine regulation, bone marrow suppression, and therapy-induced lymphopenia. Reduced Ig levels can have clinical repercussions such as increased vulnerability to infections, decreased effectiveness of vaccinations, and compromised immune monitoring. This study also looks at new and existing methods to lessen these consequences, including immunomodulatory techniques, prophylactic antibiotics, and Ig replacement treatment. Optimizing patient outcomes, striking a balance between immunological protection and oncologic efficacy, and directing future research in supportive cancer care all depend on an understanding of how humoral immunity and cancer treatment interact.
    Keywords:  DNA damage response; HDAC inhibitors; cancer immunotherapy; chemotherapy; immunoglobulin synthesis; targeted cancer therapy
    DOI:  https://doi.org/10.1177/10849785251384813
  18. Trends Mol Med. 2025 Oct 07. pii: S1471-4914(25)00217-5. [Epub ahead of print]
      Metastasis remains a major contributor to the poor prognosis for patients with cancer, primarily driven by dynamic interactions between cancer cells and the tumor microenvironment. Accumulating evidence highlights the pivotal involvement of both gut microbiota and intratumoral bacteria in cancer progression and metastatic spread. Here, we review the intricate links between microbiota and cancer metastasis, elucidating the multifaceted mechanisms by which microbial communities modulate metastatic processes. We particularly focus on the role of microbial metabolites in cancer dissemination and discuss innovative therapeutic strategies targeting the microbiome. Targeting the gut microbiota and intratumoral microecology presents a promising avenue for novel interventions aimed at mitigating cancer metastasis.
    Keywords:  cancer metastasis; cancer therapy; gut microbiota; intratumoral bacteria; microbial metabolites
    DOI:  https://doi.org/10.1016/j.molmed.2025.09.008