bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2025–06–22
fourteen papers selected by
Luca Bolliger, lxBio
  1. Editorial: Bacteriophages, prophages, and their products: regulating bacterial populations.
  2. The gut virome and human health: From diversity to personalized medicine.
  3. Storage stability prediction of spray dried Anti-Acinetobacter baumannii phage and phage cocktail powders.
  4. Viral whole-genome sequences of Pseudomonas jumbo phages, ΦNK1 and ΦBrmt, from sewage water in Japan.
  5. Bacteriophage-based veterinary products: aligning regulatory framework and development challenges for market integration.
  6. Phage tRNAs: decoding the enigma.
  7. A semi-mechanistic Pharmacokinetic/Pharmacodynamic model for quantifying phage-antibiotic synergy against Pseudomonas aeruginosa.
  8. A novel genus of virulent phage targeting Acinetobacter baumannii: Efficacy and safety in a murine model of pulmonary infection.
  9. Applications of bacteriophages in precision engineering of the human gut microbiome.
  10. Phage-antibiotic conjugates enable targeted therapeutic for infections.
  11. Biophysical and microbiological aspects of the interaction between Yersinia pestis PsaA and bacteriophage L-413C.
  12. ProtPhage: a deep learning framework for phage viral protein identification and functional annotation.
  13. Antibiotic Resistance: Revisiting Older Antibiotics for Modern Bacterial Challenges.
  14. Experimental and Computational Study of Injectable Iron(III)/Ultrashort Peptide Hydrogels: A Candidate for Ferroptosis-Induced Treatment of Bacterial Infections.
  1. Front Microbiol. 2025 ;16 1628912
    Editorial: Bacteriophages, prophages, and their products: regulating bacterial populations.
    Barbara Maciejewska, Agata Dorotkiewicz-Jach, Zuzanna Drulis-Kawa, Gamaliel López-Leal.
      
    Keywords:  antimicrobial resistance; bacteriophages; phage diversity; phage evolution; phage host interactions; phage therapy; phages; prophages
    DOI:  https://doi.org/10.3389/fmicb.2025.1628912
  2. Eng Microbiol. 2025 Mar;5(1): 100191
    The gut virome and human health: From diversity to personalized medicine.
    Rahul Harikumar Lathakumari, Leela Kakithakara Vajravelu, Anusha Gopinathan, Poornima Baskar Vimala, Vishnupriya Panneerselvam, Sujith Sri Surya Ravi, Jayaprakash Thulukanam.
      The human gut virome plays a crucial role in the gut and overall health; its diversity and regulatory functions influence bacterial populations, metabolism, and immune responses. Bacteriophages (phages) and eukaryotic viruses within the gut microbiome contribute to these processes, and recent advancements in sequencing technologies and bioinformatics have greatly expanded our understanding of the gut virome. These advances have led to the development of phage-based therapeutics, diagnostics, and artificial intelligence-driven precision medicine. The emerging field of phageomics shows promise for delivering personalized phage therapies that combat antimicrobial resistance by specifically targeting pathogenic bacteria while preserving beneficial microbes. Moreover, CRISPR-Cas systems delivered via phages have shown success in selectively targeting antibiotic resistance genes and enhancing treatment effectiveness. Phage-based diagnostics are highly sensitive in detecting bacterial pathogens, offering significant benefits for human health and zoonotic disease surveillance. This synthesis of the current knowledge highlights the pivotal role of the gut virome in regulating microbial communities and its transformative potential in personalized medicine, emphasizing its importance in advancing therapeutic and diagnostic strategies for improving health outcomes.
    Keywords:  Bacteriophage; CRISPR-Cas system; Dysbiosis; Fecal virome transplantation; Gut virome; Phage therapy
    DOI:  https://doi.org/10.1016/j.engmic.2025.100191
  3. Int J Pharm. 2025 Jun 11. pii: S0378-5173(25)00679-9. [Epub ahead of print]681 125842
    Storage stability prediction of spray dried Anti-Acinetobacter baumannii phage and phage cocktail powders.
    Andrew Foon Yu Cheng, Daniel Tim Ching Choi, Yannan Liu, Changqing Bai, Sharon Shui Yee Leung.
      Bacterial lung infections caused by Acinetobacter baumannii have traditionally been treated with oral and parental antibiotic treatments. However, the rapid emergence of multidrug-resistant (MDR) strains has led to increased mortality rates. Inhaled bacteriophage (phage) therapy, which utilizes lytic phages as therapeutic agents, has emerged as a promising alternative treatment option. However, the poor storage stability of phage products can affect their commercial viability. In this study, three anti-A. baumannii phages, including vB_AbaM-IME-AB2, vB_AbaM-IME-AB9, and vB_AbaM-IME-AB406 and their cocktail, were formulated into inhalable powders using a spray-drying technique. Two chosen excipient compositions (Formulation 1: 60% trehalose, 20% mannitol and 20% leucine, and Formulation 2: 40% trehalose, 40% mannitol and 20% leucine) were employed to stabilize phages in the powder form. The production loss of phage, particle size, particle morphology, and aerosol performance of prepared phage powders were analyzed to confirm their suitability for pulmonary delivery. Then, the feasibility of using an accelerated stability test based on the Arrhenius Equation to estimate the shelf-life of produced phage powders were demonstrated. Overall, the findings contribute to the development of inhalable phage powder formulations that can be used as a potential treatment for lung infections.
    Keywords:  Accelerated stability test; Arrhenius Equation; Bacterial lung infection; Bacteriophage; Inhaled phage therapy; Pulmonary delivery
    DOI:  https://doi.org/10.1016/j.ijpharm.2025.125842
  4. Microbiol Resour Announc. 2025 Jun 20. e0104423
    Viral whole-genome sequences of Pseudomonas jumbo phages, ΦNK1 and ΦBrmt, from sewage water in Japan.
    Jumpei Fujiki, Tomohiro Nakamura, Natsuko Ichikawa, Kohana Tamamura, Haruka Yamamoto, Yoshiaki Sakata, Keisuke Nakamura, Hidetomo Iwano.
      Jumbo phages have potentials for uncovering phage diversity. Here, we report the complete genome sequences of two Pseudomonas jumbo phages, ΦNK1 and ΦBrmt, isolated from waste water in Japan. To explore their molecular characteristics, whole phage genomes were sequenced and assembled via the short- and long-read platforms.
    Keywords:  P. aeruginosa; bacteriophage; jumbo phage; phage therapy; phikzvirus
    DOI:  https://doi.org/10.1128/mra.01044-23
  5. Biologicals. 2025 Jun 19. pii: S1045-1056(25)00038-7. [Epub ahead of print]91 101847
    Bacteriophage-based veterinary products: aligning regulatory framework and development challenges for market integration.
    Céline Antoine, David Mackay, Paul Midtlyng, Hans P Kleppen, Dušan Palić, Jean-Paul Pirnay, Damien Thiry, Etienne Thiry.
      The emergence of antimicrobial resistance renewed the interest in bacteriophages as complementary interventions to the use of antibiotics in veterinary medicine. The IABS workshop entitled "Avoiding Antimicrobial Resistance: Veterinary Use of Phages for Prevention, Therapy and Control of Bacterial Infections" brought together experts to discuss the scientific, regulatory and commercial challenges involved in bringing phage-based products to market. The biological characteristics of phages require innovative approaches for product development and regulatory approval. Dependent on their actual use, phages could be marketed as veterinary medicinal products, magistral preparations, food additives, or biocides, each classification implying different regulatory requirements and challenges, and none of which were originally intended for phage-based products. The meeting highlighted the need for regulatory harmonization to facilitate market access and allow manufacturers to choose the most appropriate regulatory pathway for their products. Recent EMA and EDQM guidelines offer some flexibility to take into account the biological nature of phages, but concerns remain about the feasibility of manufacturing phage-based products following existing rules for veterinary chemotherapeutants at commercially viable costs. Overcoming these regulatory and financial barriers is essential for the integration of phage therapy as a therapeutic option for control of bacterial infection and disease in veterinary medicine.
    Keywords:  Antimicrobial resistance; Bacteriophages; Phage therapy; Regulatory framework; Veterinary medicine
    DOI:  https://doi.org/10.1016/j.biologicals.2025.101847
  6. Trends Microbiol. 2025 Jun 17. pii: S0966-842X(25)00156-8. [Epub ahead of print]
    Phage tRNAs: decoding the enigma.
    Daan F van den Berg, Stan J J Brouns.
      The presence of tRNAs in bacteriophage genomes has intrigued scientists since their discovery in the early 1960s, as phages were believed to rely on the host tRNAs for their translation. Over the years, a multitude of hypotheses have been explored, providing evidence that phages with different lifestyles utilize tRNAs in distinct ways. In recent years, several studies have provided evidence that phage tRNAs play a crucial role in evading phage defense systems. In this review we summarize the current state of the field of phage tRNAs, highlighting their diverse roles in phage infection. We also discuss the host response to phage tRNAs and the application of this knowledge to improve phage-based therapeutics to combat bacterial infections.
    Keywords:  anti-defense genes; codon compensation; defense systems; integration site; phage tRNAs; tRNA host–phage conflict
    DOI:  https://doi.org/10.1016/j.tim.2025.05.009
  7. Expert Opin Drug Deliv. 2025 Jun 18.
    A semi-mechanistic Pharmacokinetic/Pharmacodynamic model for quantifying phage-antibiotic synergy against Pseudomonas aeruginosa.
    Omar Assafiri, Qixuan Hong, Sandra Morales, Yu-Wei Lin, Hak-Kim Chan.
       BACKGROUND: ultidrug-resistant (MDR) Pseudomonas aeruginosa is among the top three pathogens urgently needing new treatments. Phage therapy offers an alternative to antibiotics by auto-dosing and by targeting bacteria that are resistant to conventional antibiotics, and combining phages with antibiotics may overcome shortcomings of monotherapy.
    RESEARCH DESIGN AND METHODS: We developed a novel semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model based on static in vitro time-kill data evaluating ciprofloxacin (CIPRO; 0-128 µg/mL) and bacteriophage PEV31 (0.01-100 MOI) individually and in combination against MDR P. aeruginosa strain FADDI-PA001. Additionally, a Shiny-based interactive application was designed to simulate and visualize the impact of varying concentrations of phage and antibiotic treatments, facilitating real-time regimen optimization.
    RESULTS: Monotherapy with either CIPRO or PEV31 inhibited bacterial growth for less than 8 h before regrowth occurred; complete eradication was achieved only at high CIPRO concentrations (64 and 128 µg/mL). In combination (with CIPRO doses above 2 µg/mL), PEV31 and CIPRO acted synergistically, reducing bacterial levels below 102 CFU/mL at 24 h. The final PK/PD model which included a phage-bacteria-interaction term and implemented CIPRO's effect as a power-model successfully captured the observed time-kill-data for both monotherapy and combination therapy.
    CONCLUSIONS: These promising findings support further in vivo validation and mechanistic studies to advance combination therapy for MDR pathogens. Our integrated approach paves way for clinical translation.
    Keywords:  Phage-antibiotic synergy; RxODE; Semi-mechanistic PK/PD model; in vitro static time-kill assays; nlmixr2
    DOI:  https://doi.org/10.1080/17425247.2025.2520963
  8. PLoS Pathog. 2025 Jun 20. 21(6): e1013268
    A novel genus of virulent phage targeting Acinetobacter baumannii: Efficacy and safety in a murine model of pulmonary infection.
    JiaWang Wang, Huan Hu, QingQing Wang, TianZhu Zhu, XiaoHan Ren, WenQian Jiang, XueMei Hou, Jun Lin, XiaoLing Yu.
      Acinetobacter baumannii is a notable opportunistic pathogen responsible for severe hospital-acquired infections, with multidrug-resistant strains posing significant treatment challenges. Phage therapy, which employs bacteriophages as natural bacterial antagonists, has gained renewed attention as a promising solution to combat antibiotic-resistant infections. In this study, we isolated and characterized a novel virulent phage, vB_AbaS_qsb1, which specifically lyses A.baumannii. Phylogenetic and genomic analyses indicate that vB_AbaS_qsb1 is the founding member of a previously unreported genus, which we propose to name Acinibactriovirus, with Acinibactriovirus lysinus as the type species. vB_AbaS_qsb1 demonstrated robust stability across diverse temperature and pH ranges, a short latent period, and no known virulence or antibiotic resistance genes within its 54,713 bp dsDNA genome. Safety assessments showed that high-dose vB_AbaS_qsb1 induced no adverse effects in mice, with histopathology confirming its safety profile. Therapeutic experiments further indicated that vB_AbaS_qsb1 provided at least 50% protection against A.baumannii-induced pneumonia, significantly reducing bacterial loads and inflammation markers, while maintaining high phage titers in lung tissue.This study introduces vB_AbaS_qsb1 as a promising candidate for phage therapy against A.baumannii, offering both innovative insights and a valuable framework for future isolation, genomic characterization, and efficacy evaluation of phages targeting antibiotic-resistant bacteria.
    DOI:  https://doi.org/10.1371/journal.ppat.1013268
  9. Eng Microbiol. 2025 Mar;5(1): 100189
    Applications of bacteriophages in precision engineering of the human gut microbiome.
    Xiaoxian Kuang, Juntao Shen, Linggang Zheng, Yi Duan, Yingfei Ma, Elaine Lai-Han Leung, Lei Dai.
      As our understanding of the role of the gut microbiome in human diseases deepens, precision engineering of the gut microbiome using bacteriophages has gained significant attention. Herein, we review the recent advances in bacteriophage-mediated modulation of the gut microbiome, discuss approaches at the ecological and genetic levels, and summarize the challenges and strategies pertinent to each level of intervention. Drawing on the structural attributes of bacteriophages in the context of precision engineering, we examined the latest developments in the field of phage administration. Gaining a nuanced understanding of microbiome manipulation will yield tailored strategies and technologies. This could revolutionize the prevention and treatment of diseases linked to gut pathogens and offer new avenues for the therapeutic use of bacteriophages.
    Keywords:  Bacteriophages; Human gut microbiome; Microbiome engineering
    DOI:  https://doi.org/10.1016/j.engmic.2025.100189
  10. Colloids Surf B Biointerfaces. 2025 Jun 17. pii: S0927-7765(25)00390-X. [Epub ahead of print]255 114883
    Phage-antibiotic conjugates enable targeted therapeutic for infections.
    Yi Zhao, Wenxin Chen, Haixin Bi, Yanqiong Tang, Xiang Ma, Hong Li, Zhu Liu, Xue Chi, Juanjuan Li.
      Phage-antibiotic combination therapy has gained great attention as a promising approach for combating drug resistant bacterial infections. However, simply combination between antibiotics and phages shows limited efficacy for reducing antibiotic usage and preventing further multidrug resistance. Herein, we developed a phage-vancomycin conjugate, Van@vB_C4, with 1.86 ± 0.07 μg of vancomycin (Van) on 107 PFU of vB_C4. Van@vB_C4 allows the phage to deliver Van directly to the environment near host to raise localized antibiotic concentration. Van@vB_C4 demonstrates superior antibacterial activity on Van resistance Aeromonas veronii C4 (VR A. veronii C4) compared with the combination between vB_C4 and Van. Remarkably, Van@vB_C4 establishes an environment with concentrated Van around the VR A. veronii C4 biofilm, and effectively kills more than 50 % of mature biofilm cells. Furthermore, Van@vB_C4 reduces the colonization of VR A. veronii C4 in major organs of mice and alleviates the inflammatory response, achieving a potent therapeutic effect, which opens a new window for phage-antibiotic combination therapy, supporting the targeted treatment of specific antibiotic-resistant bacterial infections.
    Keywords:  Multi-drug resistance bacteria; Phage-antibiotic conjugate; Phage-antibiotic synergy; Targeted drug delivery
    DOI:  https://doi.org/10.1016/j.colsurfb.2025.114883
  11. Eur Biophys J. 2025 Jun 16.
    Biophysical and microbiological aspects of the interaction between Yersinia pestis PsaA and bacteriophage L-413C.
    Ilya Konyshev, Lyubov Dudina, Vladislav Belozerov, Sergey Ivanov, Svetlana Dentovskaya, Andrey Anisimov, Andrey Byvalov.
      There has been a great interest in developing the phage-containing remedy against plague caused by antimicrobial resistant strains of Yersinia pestis, which have been increasingly isolated in recent years from sick humans and animals. Studies thus are under way to develop a "phage cocktail", which is expected to be effective against a wide range of pathogenic strains. Our paper sheds light on the role of Y. pestis antigen PsaA in reception of the phage L-413C, which might be a possible component of such a "cocktail". Using optical trapping (OT) and atomic force microscopy (AFM), we showed that PsaA-positive cells and PsaA-coated beads or cantilevers bound more effectively to a substrate coated with L-413C rather than Pokrovskaya phage. Comparing two isogenic strains of Y. pestis (EV and EV∆psaA), we found that when bacteria and phages are co-incubated under slightly acidic pH, as if in a eukaryotic cell, PsaA-positive cells bound the phage L-413C more effectively. There is good evidence to say that L-413C may become a component of a new anti-plague therapy due to its high ability to interact with the pili-forming protein PsaA from the outer membrane of Y. pestis.
    Keywords:   Yersinia pestis ; Antigen PsaA; Atomic force microscopy; Force spectroscopy; Optical tweezers; Phage L-413C
    DOI:  https://doi.org/10.1007/s00249-025-01768-6
  12. Brief Bioinform. 2025 May 01. pii: bbaf285. [Epub ahead of print]26(3):
    ProtPhage: a deep learning framework for phage viral protein identification and functional annotation.
    Yuehua Ou, Qiyi Chen, Ningyu Zhong, Zhihua Du.
      Phages, viruses that infect bacteria, offer a promising strategy against antibiotic-resistant pathogens. Phage viral proteins (PVPs) are essential for phage-host interactions, yet their identification and functional annotation remain challenging due to high sequence diversity, limited experimental data, and class imbalance. To address these issues, we propose ProtPhage, a novel framework that leverages the ProtT5 protein language model for richer sequence representation compared to traditional methods. Additionally, ProtPhage incorporates an asymmetric loss function to mitigate class imbalance, significantly improving the prediction of the minority class "minor capsid," with an F1 score 33.07$\%$ higher than the best existing model. Extensive experiments demonstrate that ProtPhage outperforms current methods across multiple metrics, including accuracy, precision, recall, and F1 score. A case study on the Mycobacterium phage PDRPxv genome further validates its practical utility, while expanded experiments highlight its potential in phage-host prediction. By integrating advanced deep learning techniques, ProtPhage establishes a new standard for PVP identification and annotation, contributing to the broader field of computational phage biology.
    Keywords:  asymmetric loss; phage viral proteins; protein language model
    DOI:  https://doi.org/10.1093/bib/bbaf285
  13. Chem Biodivers. 2025 Jun 16. e00813
    Antibiotic Resistance: Revisiting Older Antibiotics for Modern Bacterial Challenges.
    Alberto Boretti, Bimal Banik.
      The growing challenge of antibiotic resistance necessitates a strategic re-evaluation of older antibiotics as vital antimicrobial tools. This re-assessment, while facing hurdles, reveals promising possibilities. Understanding bacterial resistance mechanisms is fundamental for effectively utilizing these legacy drugs. Older antibiotics typically have a narrower spectrum than modern ones, emphasizing careful antimicrobial stewardship to prevent overuse and further resistance. Strategies to improve their clinical value include combination therapies with newer antibiotics to overcome resistance and boost efficacy. Furthermore, repurposing and reformulating older antibiotics can enhance their activity against contemporary bacterial strains. Targeted treatment regimens focusing on specific clinical niches or bacterial species where older antibiotics remain effective, are crucial. Streptothricin F exemplifies this renewed potential, particularly against Gram-negative bacteria, a recent research focus. Despite prior concerns about its limited spectrum and resistance potential, recent findings indicate streptothricin F's re-emerging utility. This antibiotic's ability to target highly resistant Gram-negative pathogens, such as carbapenem-resistant Enterobacterales, highlights its potential as a valuable therapeutic option. This encouraging discovery underscores the need for further research into streptothricin F's role in combating drug-resistant Gram-negative pathogens, opening avenues for future investigation.
    Keywords:  Gram‐negative bacteria; antibiotics; antimicrobial resistance; combination therapy; streptothricin
    DOI:  https://doi.org/10.1002/cbdv.202400813
  14. Small Sci. 2025 Jun;5(6): 2400618
    Experimental and Computational Study of Injectable Iron(III)/Ultrashort Peptide Hydrogels: A Candidate for Ferroptosis-Induced Treatment of Bacterial Infections.
    Capucine Loth, Florent Barbault, Cécile Guégan, Flora Lemaire, Christophe Contal, Alain Carvalho, Sophie Hellé, Marie Champion, Halima Kerdjoudj, Delphine Chan-Seng, Lydie Ploux, Fouzia Boulmedais.
      Injectable hydrogels are promising candidates as local drug delivery platforms for the treatment of infected wounds. Self-assembled small peptide hydrogels are of interest due to their high biocompatibility, degradability, and ease of synthesis. This study describes the formation of an injectable hydrogel based on the self-assembly of Fmoc-FFpY (Fmoc: fluorenylmethoxycarbonyl, F: phenylalanine, pY: tyrosine phosphate) triggered by electrostatic interactions in the presence of Fe3+ ions. Stabilized by H bonding and π-π stacking, the hydrogels exhibit high mechanical stiffness with a G' (storage modulus) of ≈8000 Pa and a self-recovery up to G' ≈100 Pa. Peptide self-assembly yields β-sheets twisted into fibrillar helices of 12 nm in diameter and pitch. Molecular dynamics simulations confirm 1) the aggregation of Fmoc-FFpY in the presence of Fe3+ and the adopted secondary structure and show that 2) the aggregated Fmoc-FFpY/Fe3+ disrupts the bacterial membrane of Staphylococcus aureus and Pseudomonas aeruginosa, favoring the passive entry of Fe3+ into the pathogen. In full agreement with the simulations, the hydrogels exhibit antibacterial activity against both bacteria, likely due to the increased Fe3+ entry into the cell, resulting in enhanced production of reactive oxygen species. This work paves the way for ferroptosis-inducing treatment of bacterial infections using injectable ultrashort peptides.
    Keywords:  Fmoc‐FF; antibacterial; molecular dynamics; reactive oxygen species; siderophores
    DOI:  https://doi.org/10.1002/smsc.202400618
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