bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2025–06–15
sixteen papers selected by
Luca Bolliger, lxBio



  1. Front Cell Infect Microbiol. 2025 ;15 1597009
      Pseudomonas aeruginosa is an opportunistic pathogen causing severe infections of the lung, burn wounds and eyes. Due to its intrinsic high antibiotic resistance the bacterium is difficult to eradicate. A promising therapeutic option is the use of P. aeruginosa-specific bacteriophages. Thus, the implementation of a phage therapy requires their selection, production and systematic administration using multiple strains of the bacterial target. Here, we used 25 phages and tested their susceptibility on 141 different P. aeruginosa strains isolated from patients with different types of infection. Comparative host spectrum analyses were carried out using double agar overlay plaque assay (DPA) and planktonic killing assay (PKA), which resulted in 70% of the cases in the same host range. All phages were assigned to known phage genera, but some of the phages are new species. Isolated members of the genera Pakpunavirus, Pbunavirus (myoviruses), Pawinskivirus, Elvirus (myoviruses, jumbo phages), Litunavirus and Bruynoghevirus (podoviruses) demonstrated great therapeutic potential due to strong lysis behavior on diverse strains. Seven phages were excluded for therapeutic purposes due to genetic determinants that confer lysogenicity. Due to automation with lower time expenditure in execution and analysis, PKA has the higher potential for implementation in diagnostics. Finally, different combinations of phages were tested in silico with various P. aeruginosa strains. Highly efficient phage combinations eradicating multiple P. aeruginosa strains were found. Thus, a solid basis for the development of a broad host range phage therapy was laid.
    Keywords:  Pseudomonas aeruginosa; antibiotic resistance; bacteriophages; phage selection; phage susceptibility testing
    DOI:  https://doi.org/10.3389/fcimb.2025.1597009
  2. Front Cell Infect Microbiol. 2025 ;15 1611857
      Phage therapy is emerging as a promising strategy against the growing threat of antimicrobial resistance, yet phage and bacteria are incredibly diverse and idiosyncratic in their interactions with one another. Clinical applications of phage therapy often rely on a process of manually screening collections of naturally occurring phages for activity against a specific clinical isolate of bacteria, a labor-intensive task that is not guaranteed to yield a phage with optimal activity against a particular isolate. Herein, we review recent advances in artificial intelligence (AI) approaches that are advancing the study of phage-host interactions in ways that might enable the design of more effective phage therapeutics. In light of concurrent advances in synthetic biology enabling rapid genetic manipulation of phages, we envision how these AI-derived insights could inform the genetic optimization of the next generation of synthetic phages.
    Keywords:  artificial intelligence; gene discovery; machine learning; phage engineering; phage specificity; phage therapy; synthetic biology
    DOI:  https://doi.org/10.3389/fcimb.2025.1611857
  3. Mol Biol Rep. 2025 Jun 09. 52(1): 571
      Pseudomonas aeruginosa is a gram-negative clinical pathogen, particularly affecting immunocompromised patients, those with cystic fibrosis, and burn victims. It causes chronic infections, especially in hospital settings, and is a significant contributor to nosocomial infections. Its capacity to create biofilms resistant to antibiotics is the reason for its infamous persistence in clinical settings. P. aeruginosa infections can affect any area of the body because the bacteria's biofilm enables it to stick to any surface, living or non-living. One of the primary clinical challenges in treating P. aeruginosa biofilm is its noteworthy resistance to many classes of antibiotics. The bacterium's ability to acquire resistance through efflux pumps, beta-lactamase production, and genetic mutations complicates treatment options. Recently, multidrug- resistant (MDR) strains of P. aeruginosa are becoming increasingly prevalent, limiting the efficacy of traditional antibiotics and leading to the need for alternative therapies. There is an ongoing need for novel treatment options, including bacteriophage therapy, antimicrobial peptides, and vaccines. The rapid adaptability of P. aeruginosa and its ability to develop resistance underscores the importance of continued research into new therapeutic strategies. This review discusses the various therapeutic strategies like; antimicrobial therapy, targeting efflux pumps and biofilms of P. aeruginosa, phage therapy, immunotherapy and nanotechnology to explore the mechanisms, through which antimicrobial compounds interact with biofilm structures and the bacteria within.
    Keywords:   Pseudomonas aeruginosa ; Antimicrobial peptides; Bacteriophage; Biofilm; Multidrug resistance
    DOI:  https://doi.org/10.1007/s11033-025-10683-0
  4. J Appl Microbiol. 2025 Jun 11. pii: lxaf144. [Epub ahead of print]
       AIMS: In phage therapy case studies, 1-3 bacteria isolates are typically tested against phages (phagogram). However, as bacteria populations differ in their susceptibility to phages and antibiotics, the strains selected may not represent how the infecting population will respond to treatment. Our aim was to assess whether the effects of phage on single or a mix of isolates in vitro show more comparable results to that observed during a clinical case study.
    METHODS AND RESULTS: The patient presented with a methicillin resistant Staphylococcus aureus infection (MRSA). In this previously published case study, phage therapy alongside antibiotics rapidly cleared blood cultures of bacteria while localised regions, including the lungs, took longer to clear of bacteria. In this follow-up study, mixed isolates were more likely to persist than single isolates in vitro, more closely representing the lung, but not blood, infections. These results may reflect the different degrees of genetic diversity of the infecting bacteria in these sites.
    CONCLUSIONS: For this patient, phage therapy predictions were significantly affected by whether we used mixed versus single isolates, but the predictive precision depended on the site of in vivo infection.
    Keywords:  applied microbiology; bacteriophages; clinical microbiology; microbial ecology; staphylococcus
    DOI:  https://doi.org/10.1093/jambio/lxaf144
  5. Microbiol Spectr. 2025 Jun 10. e0288224
      The rise of antibiotic-resistant bacteria has necessitated the development of alternative therapeutic strategies, such as bacteriophage therapy, where viruses infect bacteria, reducing bacterial burden. However, rapid bacterial resistance to phage treatment remains a critical challenge, potentially leading to failure. Phage steering, which leverages the evolutionary dynamics between phage and bacteria, offers a novel solution by driving bacteria to evolve away from virulence factors or resistance mechanisms. In this study, we examined whether phage steering using bacteriophage Luz19 could function in the presence of a competing pathogen, Staphylococcus aureus (SA) (USA300), while targeting Pseudomonas aeruginosa (PAO1). Through in vitro co-evolution experiments with and without the competitor, we observed that Luz19 consistently steered P. aeruginosa away from the Type IV pilus (T4P), a key virulence factor, without interference from SA. Genomic analyses revealed mutations in T4P-associated genes, including pilR and pilZ, which conferred phage resistance. Our findings suggest that phage steering remains effective even in polymicrobial environments, providing a promising avenue for enhancing bacteriophage therapy efficacy in complex infections.IMPORTANCEPhage steering-using phages that bind essential virulence or resistance-associated structures-offers a promising solution by selecting for resistance mutations that attenuate pathogenic traits. However, it remains unclear whether this strategy remains effective in polymicrobial contexts, where interspecies interactions may alter selective pressures. Here, we demonstrate that Pseudomonas aeruginosa evolves phage resistance via loss-of-function mutations in Type IV pilus (T4P) when challenged with the T4P-binding phage Luz19 and that this evolutionary trajectory is preserved even in the presence of a competing pathogen, Staphylococcus aureus. Phage resistance was phenotypically confirmed via twitching motility assays and genotypically via whole-genome sequencing. These findings support the robustness of phage steering under interspecies competition, underscoring its translational potential for managing complex infections-such as those seen in cystic fibrosis-where microbial diversity is the norm.
    Keywords:  bacteriophage evolution; bacteriophage therapy; bacteriophages; steering; virulence
    DOI:  https://doi.org/10.1128/spectrum.02882-24
  6. Biofilm. 2025 Jun;9 100288
      Implant-associated infections remain a critical challenge due to the presence of biofilm-forming bacteria, which enhance tolerance to conventional treatments. This study investigates the efficacy of a tri-enzymatic cocktail (TEC; DNA/RNA endonuclease, endo-14-β-d-glucanase, β-N-acetylhexosaminidase) targeting biofilm matrix components combined with supratherapeutic doses of antibiotics encapsulated in a thermosensitive hydrogel (poloxamer P407) for local administration. In vitro, the hydrogel formulation enabled controlled release of active agents over 12 h. Vancomycin and TEC co-formulated in hydrogel achieved up to 3.8 Log10 CFU count reduction and 80 % biofilm biomass reduction on MRSA biofilms grown on titanium coupons, demonstrating enhanced efficacy as compared to individual active agents, with 1.3-3.2 log10 additional killing. Fluoroquinolone efficacy remained unchanged by enzyme addition. In vivo, in a model of tissue cages containing titanium beads implanted in the back of guinea pigs, hydrogel-delivered vancomycin maintained therapeutic levels for seven days. Coupled with an intraperitoneal administration of vancomycin for 4 days, a single local administration of hydrogel containing both vancomycin and TEC was more effective than hydrogels containing either vancomycin or TEC, achieving an additional 2.1 Log10 CFU reduction compared to local vancomycin, 2.3 Log10 compared to local TEC, and 4.3 Log10 compared to systemic vancomycin treatment alone. However, partial regrowth occurred at later stages, indicating room for further optimization. Nevertheless, these findings already underscore the potential of combining a high dose of antibiotic with an enzymatic cocktail in a sustained-release hydrogel delivery system as a promising strategy for improving the management of biofilm-associated implant infections.
    Keywords:  Biofilm; Enzymatic cocktail; Implant infection; Poloxamer P407 hydrogel; Tissue cage model; Vancomycin
    DOI:  https://doi.org/10.1016/j.bioflm.2025.100288
  7. Molecules. 2025 May 26. pii: 2323. [Epub ahead of print]30(11):
      Photocatalysis and photodynamic therapy have been increasingly used in the management of diabetic foot ulcers (DFUs), and their integration into increasingly innovative treatment protocols enables effective infection control. Advanced techniques such as antibacterial photodynamic therapy (aPDT), liposomal photocatalytic carriers, nanoparticles, and nanomotors-used alone, in combination, or with the addition of antibiotics, lysozyme, or phage enzymes-offer promising solutions for wound treatment. These approaches are particularly effective even in the presence of comorbidities such as angiopathies, neuropathies, and immune system disorders, which are common among diabetic patients. Notably, the use of combination therapies holds great potential for addressing challenges within diabetic foot ulcers, including hypoxia, poor circulation, high glucose levels, increased oxidative stress, and rapid biofilm formation-factors that significantly hinder wound healing in diabetic patients. The integration of modern therapeutic strategies is essential for effective clinical practice, starting with halting infection progression, ensuring its effective eradication, and promoting proper tissue regeneration, especially considering that, according to the WHO, 830 million people worldwide suffer from diabetes.
    Keywords:  antibacterial photodynamic therapy; biofilm prevention; diabetic foot ulcers; diabetic wound; liposomes; nanoparticles; oxidative stress; photocatalysis; photosensitizer; tissue regeneration
    DOI:  https://doi.org/10.3390/molecules30112323
  8. Trends Microbiol. 2025 Jun 06. pii: S0966-842X(25)00155-6. [Epub ahead of print]
      Research on the human gut microbiome is expanding rapidly; yet, most published studies focus on populations from high-income regions such as North America and Europe. Underrepresentation of populations from low- and middle-income countries in the microbiome literature limits the generalizability of microbiome-health associations. These challenges are compounded by computational barriers, including biases in reference databases, nonrepresentative metadata, and infrastructure limitations in low- and middle-income countries. However, recent efforts in large-scale global sampling have begun to address these problems. This review provides recommendations for future research efforts applying computational analysis to global microbiome data, including guidelines to initiate and maintain equitable partnerships, identify representative datasets, overcome technical limitations, and contextualize results at the global scale.
    Keywords:  global health; global microbiome diversity; microbiome; next-generation sequencing; reference genomes; research equity
    DOI:  https://doi.org/10.1016/j.tim.2025.05.008
  9. NPJ Antimicrob Resist. 2025 Jun 11. 3(1): 50
      Antimicrobial resistance (AMR) is a serious global threat projected to cause 10 million deaths annually by 2050. Antibiotics are becoming ineffective, leading to poor health outcomes and economic burden. Despite the urgent need, scientific, economic, and regulatory challenges hinder antibiotic development, causing major companies to exit the field. This review explores the AMR crisis, challenges in antibiotic development, particularly for Gram-negative bacteria, and potential solutions to revitalise the antibiotic pipeline.
    DOI:  https://doi.org/10.1038/s44259-025-00123-1
  10. Proc Natl Acad Sci U S A. 2025 Jun 17. 122(24): e2426508122
      In recent years, the number of newly discovered systems that bacteria use to combat bacteriophages is increasing at an impressive rate. To obtain mechanistic insights into several antiphage systems identified in previous studies, we isolated 66 phage escape mutants which had become insensitive to 13 distinct, plasmid-encoded lactococcal phage resistance systems (i.e. Rhea, Kamadhenu, Rugutis, Audmula, PARIS, type II CBASS, Septu, AbiA, AbiB, AbiD/F, AbiG, AbiJ, AbiP). Genome analysis of these phage escape mutants identified a total of 15 mutated genes. Six of the encoded proteins appear to activate specific antiphage systems. Furthermore, AbiA escape mutants were found to be insensitive to AbiJ, while distinct antiphage systems (AbiG and AbiP) were observed to be activated by a major phage tail protein, indicating mechanistic commonalities. PARIS homologues encoded by members of different bacterial genera appear to share similar sensing mechanisms, whereas our data indicate mechanistic differences between Septu homologues from different genera. Based on our escape mutant sequence analysis, previously predicted domains, and experimental data using the purified endolysin of phage c2, we propose that Audmula modifies the cell wall of the host bacterium, delaying cell lysis and release of progeny phages, protecting the host cell by a heretofore unknown mode of action. The obtained advances in our understanding of lactococcal antiphage mechanisms provide fundamental insights into phage-host interactions, which undoubtedly benefits the dairy industry but may also be useful for biotechnological or biomedical applications.
    Keywords:  Lactococcus; activation; escape mutants; lactic acid bacteria; phage defense
    DOI:  https://doi.org/10.1073/pnas.2426508122
  11. Cancer Biother Radiopharm. 2025 Jun 12.
      Recently, exosomes, or "natural nanoparticles," have been considered as potential drug delivery methods. Due to exosome carriers' natural properties, exosome-mediated drug delivery systems (DDSs) are efficient cancer treatments. Exosomes, small membrane vesicles from many cell types, can transfer phytoconstituents, proteins, nucleic acids, and small molecule medicines across biological boundaries. Recent DDS advances have improved this potential using plant-derived exosomes (PDEs), which are biocompatible and low toxic. PDEs have anticancer effects, especially in the context of conventional treatment resistance, untargeted toxicity, and response variability. This review fills a gap by discussing the latest findings and offering new perspectives on exosome drug delivery in cancer. The study summarizes isolation and loading approaches such as ultracentrifugation and immunological isolation and the characterization parameters for the formulation of exosomes. The exosome-based DDSs are discussed in depth, along with the emphasis on PDEs. The article highlights emerging trends and challenges, including molecular targets and ongoing clinical trials, during the past decade that are critically relevant to the current scenario. Nanotechnology and personalized medicine could improve and lower the cost of exosome-mediated cancer treatment. While the preclinical data have been encouraging, clinical applications of exosome-based therapies are continuing to evolve in its early stages, and some of the problems include scalability, purification, and regulatory compliance.
    Keywords:  bioavailability; cancer; cargo loading; extracellular vesicles; nano drug delivery; plant-derived exosomes
    DOI:  https://doi.org/10.1089/cbr.2025.0050
  12. Am J Clin Dermatol. 2025 Jun 11.
      Recent advancements in wound healing are reshaping clinical practice by integrating dermatology, cutaneous microbiome research, and technology. This article discusses new diagnostic tools, such as imaging devices and microbial composition analysis, that enhance our understanding of wound environments. It highlights the importance of wound bed preparation and explores innovative treatment methods for optimal wound healing, including debridement techniques like ultrasound-assisted methods, hydrosurgery, and larval therapy. The evolution of wound management is further illustrated through the use of cellular and acellular matrix products and cellular therapies involving whole blood products. We also present the latest insights on the wound microbiome and antimicrobial treatments, including advanced dressings and antibiofilm surfactants. Finally, the potential of gene therapy for complex conditions like epidermolysis bullosa is discussed as a promising model for advancing wound healing. This review synthesizes current research to improve dermatological practices and patient outcomes in wound care.
    DOI:  https://doi.org/10.1007/s40257-025-00953-9
  13. Int J Pharm. 2025 Jun 07. pii: S0378-5173(25)00655-6. [Epub ahead of print]681 125818
      Polymeric hydrogels are hydrophilic polymer networks capable of absorbing and retaining large amounts of water or biological fluids, making them highly suitable for biomedical applications. This manuscript presents a comprehensive overview of their fundamental properties, including swelling behavior, biocompatibility, biodegradability, mechanical strength, crosslinking density, and stimuli-responsiveness, which collectively determine their clinical performance. A variety of natural and synthetic polymers are explored in the design of hydrogels, each offering distinct advantages for specific biomedical uses. The clinical versatility of polymeric hydrogels is examined across multiple application areas, including wound healing, bone regeneration, joint therapy, tissue engineering, ophtalmologie, dental medicine, drug delivery systems, and hearing-related treatments. Furthermore, this review presents real-world hydrogel-based products already in clinical use and highlights current innovations and clinical trials that are extending the frontiers of hydrogel technology. Despite these advancements, challenges like scalability, reproducibility in clinical outcomes, regulatory hurdles, and long-term safety are critically assessed, along with emerging opportunities that may shape the future of hydrogel-based therapies. By integrating materials science with clinical perspectives, this review aims to support the development and translation of advanced polymeric hydrogel systems into modern medicine.
    Keywords:  Drug Delivery; Polymeric Hydrogels; Regenerative Medicine; Tissue Engineering; Wound Healing
    DOI:  https://doi.org/10.1016/j.ijpharm.2025.125818
  14. J Appl Microbiol. 2025 Jun 12. pii: lxaf146. [Epub ahead of print]
       AIMS: Bacteriophages have emerged as a therapeutic option to treat multidrug-resistant (MDR) bacteria, including carbapenem-resistant Acinetobacter baumannii (CRAB). This study reports the identification and characterisation of bacteriophage D2SVT, which was effective and specific against CRAB.
    METHODS AND RESULTS: Thirty-five collected samples were tested for antibacterial activity against CRAB. The D2SVT phage exhibited significant lytic activity, forming larger zones and clearer plaques than the Acinetobacter phage PBAB132 in spot assays. Growth kinetics assays, CFU/ml plating, 3,5-Dinitrosalicylic acid assays, reactive oxygen species (ROS) assays, protein carbonylation assays, and membrane damage assays confirmed D2SVT's specificity to CRAB and its superior efficacy over PBAB132. Characterisation using scanning electron microscopy, transmission electron microscopy, confocal microscopy, and flow cytometry revealed CRAB membrane disruption, reduced viability, and phage-cell interaction. D2SVT also exhibited anti-biofilm activity, as observed in scanning electron microscopy (SEM) analysis. D2SVT also reduced the infection of CRAB in the A549 cell line. No non-specific effects were observed on E. coli, B. subtilis, and Lactobacillus. Transmission electron microscopy (TEM) analysis classified D2SVT as a short-tailed phage with icosahedral capsid geometry (hexagonal head structure), placing it within the Caudoviricetes family. Whole genome sequencing has identified it as a phage that is closely related to phage PhiE11, and its sequence was submitted to the National Center for Biotechnology Information (NCBI).
    CONCLUSIONS: Bacteriophage D2SVT is highly specific and effective against CRAB, demonstrating strong lytic activity and anti-biofilm properties that support its potential for phage therapy.
    Keywords:   Acinetobacter baumannii ; ESKAPE pathogens; antibiofilm; bacteriophage; multi-drug resistance
    DOI:  https://doi.org/10.1093/jambio/lxaf146
  15. J Pharm Bioallied Sci. 2025 May;17(Suppl 1): S59-S62
      Personalized medicine creates revolutionary treatments for rare genetic disorders through medicine that adjusts to individual genetic information. The development of next-generation sequencing and whole-genome sequencing through genomic research has made precise medical diagnoses along with personalized treatments possible. The current therapies using CRISPR-Cas9 and gene therapy methods tend to fix harmful mutations effectively. Biomarker discovery, along with precise diagnostic techniques enables doctors to develop precise treatment methods through targeted therapeutic approaches. The ongoing revolution in rare disease management through personalized medicine faces hurdles of affordability and barrier to access and ethical questions but continues to create better individualized therapeutic solutions.
    Keywords:  CRISPR-Cas9; genetic profiling; multi-omics; personalized medicine; rare genetic disorders
    DOI:  https://doi.org/10.4103/jpbs.jpbs_583_25