bims-fagtap Biomed News
on Phage therapies and applications
Issue of 2025–08–17
thirteen papers selected by
Luca Bolliger, lxBio
  1. Recent insights on challenges encountered with phage therapy against gastrointestinal-associated infections.
  2. Phage Therapy: A Targeted Solution for Brucellosis.
  3. Phage Host Range Expansion Through Directed Evolution on Highly Phage-Resistant Strains of Klebsiella pneumoniae.
  4. Synthetic and Functional Engineering of Bacteriophages: Approaches for Tailored Bactericidal, Diagnostic, and Delivery Platforms.
  5. Antimicrobial PLGA-based micro/nanoparticles for nanomedicine of pulmonary diseases: From respiratory infections to pulmonary hypertension and fibrosis.
  6. Efficacy of a commercial bacteriophage cocktail against planktonic cells and both thin and thick biofilms of skin pathogens, measured using isothermal microcalorimetry.
  7. Charting a phage genome atlas.
  8. Application of Phage-Modified Conjugated Polymer-Based Nanoparticles in the Disruption of Bacterial Biofilms.
  9. Advancements in Hydrogels: A Comprehensive Review of Natural and Synthetic Innovations for Biomedical Applications.
  10. Quaternized chitosan derivatives inhibit growth and affect biofilm formation of Staphylococcus aureus.
  11. Wound dressings protect against bacterial environment: results of a prospective clinical study.
  12. Treatment of chronic wounds with cold plasma: a randomised, single-blind, placebo-controlled clinical study.
  13. Clinical Relevance of PCR Versus Culture in Urinary Tract Infections Diagnosis: Quantification Cycle as a Predictor of Bacterial Load.
  1. Gut Pathog. 2025 Aug 11. 17(1): 60
    Recent insights on challenges encountered with phage therapy against gastrointestinal-associated infections.
    Reem A Youssef, Masarra M Sakr, Rania I Shebl, Khaled M Aboshanab.
      
    Keywords:  Antimicrobial resistance; Bacterial gastroenteritis; Challenges; Phage therapy
    DOI:  https://doi.org/10.1186/s13099-025-00735-y
  2. Vector Borne Zoonotic Dis. 2025 Aug 11.
    Phage Therapy: A Targeted Solution for Brucellosis.
    Bahareh Lashtoo Aghaee, Mohammad Yousef Alikhani, Sima Kazemi, Mohammad Ahmadyousefi, Willem B van Leeuwen, Mona Nasaj.
      Background: Brucellosis is a widespread zoonotic bacterial infection that affects over 500,000 people annually, with significant economic losses in the livestock industry, particularly in endemic regions such as the Middle East, Asia, and parts of Africa and Latin America. Despite standard antibiotic treatments, relapse rates remain as high as 10%-15%, highlighting the limitations of current therapeutic options. Objective: Phage therapy, which uses bacteriophages to selectively target and lyse Brucella spp. bacteria, offers a promising approach for managing brucellosis. Methods: This paper explores the current understanding of brucellosis, highlighting the impact on animal and human health, and reviews the mechanisms and efficacy of bacteriophages against Brucella spp.Results:Key factors, such as phage specificity, immune modulation, and recent advancements in phage encapsulation, are discussed as strategies to enhance treatment efficacy. Conclusion: This review aims to explore emerging alternative therapies beyond conventional antibiotics, focusing on approaches such as immunotherapy, bacteriophage therapy, and novel vaccine strategies to improve clinical outcomes and reduce disease burden.
    Keywords:  Brucella infections; bacteriophage therapy; zoonosis
    DOI:  https://doi.org/10.1177/15303667251367519
  3. Int J Mol Sci. 2025 Aug 06. pii: 7597. [Epub ahead of print]26(15):
    Phage Host Range Expansion Through Directed Evolution on Highly Phage-Resistant Strains of Klebsiella pneumoniae.
    Kevin A Burke, Tracey L Peters, Olga A Kirillina, Caitlin D Urick, Bertran D Walton, Jordan T Bird, Nino Mzhavia, Martin O Georges, Paphavee Lertsethtakarn, Lillian A Musila, Mikeljon P Nikolich, Andrey A Filippov.
      Multidrug-resistant (MDR) strains of Klebsiella pneumoniae present an acute threat as they continue to disseminate globally. Phage therapy has shown promise as a powerful approach to combat MDR infections, but narrow phage host ranges make development of broad acting therapeutics more challenging. The goal of this effort was to use in vitro directed evolution (the "Appelmans protocol") to isolate K. pneumoniae phages with broader host ranges for improved therapeutic cocktails. Five myophages in the genus Jiaodavirus (family Straboviridae) with complementary activity were mixed and passaged against a panel of 11 bacterial strains including a permissive host and phage-resistant clinical isolates. Following multiple rounds of training, we collected phage variants displaying altered specificity or expanded host ranges compared with parental phages when tested against a 100 strain diversity panel of K. pneumoniae. Some phage variants gained the ability to lyse previously phage-resistant strains but lost activity towards previously phage-susceptible strains, while several variants had expanded activity. Whole-genome sequencing identified mutations and recombination events impacting genes associated with host tropism including tail fiber genes that most likely underlie the observed changes in host ranges. Evolved phages with broader activity are promising candidates for improved K. pneumoniae therapeutic phage cocktails.
    Keywords:  Appelmans protocol; Jiaodavirus; Klebsiella pneumoniae; defined mutations and recombination events; host range expansion; phage cocktail improvement; phage training
    DOI:  https://doi.org/10.3390/ijms26157597
  4. Molecules. 2025 Jul 25. pii: 3132. [Epub ahead of print]30(15):
    Synthetic and Functional Engineering of Bacteriophages: Approaches for Tailored Bactericidal, Diagnostic, and Delivery Platforms.
    Ola Alessa, Yoshifumi Aiba, Mahmoud Arbaah, Yuya Hidaka, Shinya Watanabe, Kazuhiko Miyanaga, Dhammika Leshan Wannigama, Longzhu Cui.
      Bacteriophages (phages), the most abundant biological entities on Earth, have long served as both model systems and therapeutic tools. Recent advances in synthetic biology and genetic engineering have revolutionized the capacity to tailor phages with enhanced functionality beyond their natural capabilities. This review outlines the current landscape of synthetic and functional engineering of phages, encompassing both in-vivo and in-vitro strategies. We describe in-vivo approaches such as phage recombineering systems, CRISPR-Cas-assisted editing, and bacterial retron-based methods, as well as synthetic assembly platforms including yeast-based artificial chromosomes, Gibson, Golden Gate, and iPac assemblies. In addition, we explore in-vitro rebooting using TXTL (transcription-translation) systems, which offer a flexible alternative to cell-based rebooting but are less effective for large genomes or structurally complex phages. Special focus is given to the design of customized phages for targeted applications, including host range expansion via receptor-binding protein modifications, delivery of antimicrobial proteins or CRISPR payloads, and the construction of biocontained, non-replicative capsid systems for safe clinical use. Through illustrative examples, we highlight how these technologies enable the transformation of phages into programmable bactericidal agents, precision diagnostic tools, and drug delivery vehicles. Together, these advances establish a powerful foundation for next-generation antimicrobial platforms and synthetic microbiology.
    Keywords:  CRISPR-Cas systems; antimicrobial delivery platforms; bacteriophage engineering; cell-free TXTL systems; host range expansion; non-replicative phage; phage assembly and rebooting; phage recombineering; retron-mediated editing; synthetic biology
    DOI:  https://doi.org/10.3390/molecules30153132
  5. Int J Pharm. 2025 Aug 07. pii: S0378-5173(25)00891-9. [Epub ahead of print]683 126054
    Antimicrobial PLGA-based micro/nanoparticles for nanomedicine of pulmonary diseases: From respiratory infections to pulmonary hypertension and fibrosis.
    Sareh Kakavandi, Iman Zare, Mojdeh Mirshafiei, Mingzhen Zhang, Kai Zheng, Chowon Kim, Fariborz Sharifianjazi, Leila Akhvlediani, Ketevan Tavamaishvili, Meng Yu, Heemin Kang, Pooyan Makvandi.
      Pulmonary diseases are one of the most important causes of mortality worldwide, and the number of these patients is increasing annually. Therefore, the recent development of nanomedicine approaches holds promise for a bright future in this field, considering the limitations of previous treatments. One of the most important nanoparticles in this field is PLGA, which offers special properties such as tunable disintegration, controlled drug release, biocompatibility, antimicrobial properties and non-inflammatory inhalation, which make it superior to other polymers for biomedical and pulmonary application including positive impact on a variety of pulmonary diseases such as pulmonary fibrosis and hypertension, respiratory infections and lung injury. As a result, has the potential to revolutionize the treatment of these diseases by improving treatment outcomes and increasing the quality of life of patients. However, further research is needed to optimize their formulation parameters, address technical challenges, and translate these strategies into clinical practice. The purpose of this study is to investigate the effective role of this unique nanoparticle in potential pulmonary delivery, different types of pulmonary diseases (lung injury, pulmonary fibrosis and hypertension) and also the positive effect of PLGA on different bacterial and viral involved in respiratory infection (phage therapy, and antibiotic therapy), and the challenges raised in the direction of more awareness in this area.
    Keywords:  Antibacterial activities; Nanomedicine; PLGA; Pulmonary diseases; Respiratory infections
    DOI:  https://doi.org/10.1016/j.ijpharm.2025.126054
  6. Front Microbiol. 2025 ;16 1608243
    Efficacy of a commercial bacteriophage cocktail against planktonic cells and both thin and thick biofilms of skin pathogens, measured using isothermal microcalorimetry.
    Tecla Lafranca, Gernot Bonkat, Malte Rieken, Olivier Braissant.
       Introduction: Skin and soft tissue infections are frequent and often require antibiotic treatment. However, for mild and self-limiting lesions, bacteriophage therapy could be an interesting treatment option that limits the use of antimicrobials and helps avoid the development of resistance. Still, very little is known about the efficacy of commercial phage cocktails against the biofilms encountered in these lesions. In this study, we investigated the use of a commercial phage cocktail against Staphylococci and Streptococci grown planktonically in thin and thick biofilms.
    Methods: Isothermal microcalorimetry was used to monitor the metabolic activity of planktonic cells, as well as cells grown in thin or thick biofilms of common skin pathogens (Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus agalactiae), when exposed to the commercial phage cocktail.
    Results: The use of phages against sensitive strains showed a rapid decrease in metabolic activity in planktonic cells. However, when applied to a thin biofilm, the effect was already less, although it was still important. Finally, no effect was visible on thick and mature biofilms.
    Conclusion: The efficacy of bacteriophage cocktails is limited by the thickness and maturation of biofilms. In the case of skin and soft tissue infections, especially for chronic wounds, it might be necessary to mechanically remove and disrupt the biofilm through mechanical debridement to enable the phage product to be effective.
    Keywords:  Staphylococcus; biofilms; isothermal calorimetry; phage (bacteriophage); phage therapies
    DOI:  https://doi.org/10.3389/fmicb.2025.1608243
  7. Cell Host Microbe. 2025 Aug 13. pii: S1931-3128(25)00273-2. [Epub ahead of print]33(8): 1311-1312
    Charting a phage genome atlas.
    Shelby E Andersen, Breck A Duerkop.
      Deciphering the relationship between bacteriophage genotypes and phenotypes has been limited by a lack of genetic tractability and high-throughput screening methods. In this issue of Cell Host & Microbe, Chen et al. establish PhageMaP for generating phage mutant libraries to systematically interrogate phage gene function.
    DOI:  https://doi.org/10.1016/j.chom.2025.07.001
  8. ACS Appl Bio Mater. 2025 Jul 26.
    Application of Phage-Modified Conjugated Polymer-Based Nanoparticles in the Disruption of Bacterial Biofilms.
    Wenyu Cai, Lu Hao, Qi Shao, Hailin Zhou, Ziyao He, Lulu Zhu, Dong Gao, Chengfen Xing.
      Photothermal antimicrobial therapy (PTT) has demonstrated significant potential in eradicating biofilms and reducing bacterial resistance. However, a major drawback of traditional PTT is the lack of selectivity, which reduces the efficiency and can cause substantial damage to healthy cells and tissues. Therefore, improving the precision of photochemical therapy against pathogenic bacteria is critical. This study leverages the high targeting specificity of bacteriophages to develop a bacteriophage-modified, near-infrared-responsive conjugated polymer nanosystem for targeted elimination of bacteria and effective biofilm disruption. The developed nanosystem integrates multiple functions, including bacterial targeting, photothermal sterilization, and drug delivery. In vitro antibacterial and biofilm assays demonstrate that the system exhibits enhanced targeting precision and effective bactericidal activity against Pseudomonas aeruginosa. This study highlights the potential of such a multifunctional approach to address bacterial resistance and advance therapeutic applications in combating bacterial infections.
    Keywords:  bacterial biofilms; bacteriophage; conjugated polymer; photochemical therapy; specific targeting
    DOI:  https://doi.org/10.1021/acsabm.5c00933
  9. Polymers (Basel). 2025 Jul 24. pii: 2026. [Epub ahead of print]17(15):
    Advancements in Hydrogels: A Comprehensive Review of Natural and Synthetic Innovations for Biomedical Applications.
    Adina-Elena Segneanu, Ludovic Everard Bejenaru, Cornelia Bejenaru, Antonia Blendea, George Dan Mogoşanu, Andrei Biţă, Eugen Radu Boia.
      In the rapidly evolving field of biomedical engineering, hydrogels have emerged as highly versatile biomaterials that bridge biology and technology through their high water content, exceptional biocompatibility, and tunable mechanical properties. This review provides an integrated overview of both natural and synthetic hydrogels, examining their structural properties, fabrication methods, and broad biomedical applications, including drug delivery systems, tissue engineering, wound healing, and regenerative medicine. Natural hydrogels derived from sources such as alginate, gelatin, and chitosan are highlighted for their biodegradability and biocompatibility, though often limited by poor mechanical strength and batch variability. Conversely, synthetic hydrogels offer precise control over physical and chemical characteristics via advanced polymer chemistry, enabling customization for specific biomedical functions, yet may present challenges related to bioactivity and degradability. The review also explores intelligent hydrogel systems with stimuli-responsive and bioactive functionalities, emphasizing their role in next-generation healthcare solutions. In modern medicine, temperature-, pH-, enzyme-, light-, electric field-, magnetic field-, and glucose-responsive hydrogels are among the most promising "smart materials". Their ability to respond to biological signals makes them uniquely suited for next-generation therapeutics, from responsive drug systems to adaptive tissue scaffolds. Key challenges such as scalability, clinical translation, and regulatory approval are discussed, underscoring the need for interdisciplinary collaboration and continued innovation. Overall, this review fosters a comprehensive understanding of hydrogel technologies and their transformative potential in enhancing patient care through advanced, adaptable, and responsive biomaterial systems.
    Keywords:  biomedical applications; drug delivery systems; hydrogels; polymers; regenerative medicine
    DOI:  https://doi.org/10.3390/polym17152026
  10. Sci Rep. 2025 Aug 12. 15(1): 29606
    Quaternized chitosan derivatives inhibit growth and affect biofilm formation of Staphylococcus aureus.
    Alex Miranda, Nichole D Brandquist, Kristen Johnson, Elena Muldiiarova, Aleksandr Fadeev, Mahboubeh Ghanbari, Jennifer L Endres, Kenneth W Bayles, Jason MacTaggart, Denis Svechkarev, Marat R Sadykov, Yury Salkovskiy.
      Antimicrobial resistance (AMR) poses a global health threat, severely impeding the effective treatment of bacterial infections and jeopardizing the safety of routine medical procedures. Methicillin-resistant Staphylococcus aureus (MRSA) is particularly problematic because of its resistance to beta-lactams and the ability to form resilient biofilms. Conventional antibiotics, including last-resort options, have serious side effects and may contribute to further resistance. Chitosan, a natural biopolymer, offers a promising alternative due to its biocompatibility and antimicrobial properties, though its effectiveness against biofilms is limited. Recent studies suggest that increasing the positive charge density and adding hydrophobic moieties to chitosan, can enhance its antimicrobial properties. In this work, the antibacterial activity of quaternized chitosan derivatives against AMR S. aureus strains was assessed. Quaternization of chitosan's amino group and introduction of hydrophobic side chains was found to significantly inhibit bacterial growth in both methicillin-sensitive (MSSA) and MRSA strains. Notably, nanofibrous materials composed of polyethylene oxide and hexyl-modified chitosan demonstrate alterations in S. aureus biofilm development, leading to significant accumulation of dead cells. Combined, these results highlight the potential of modified chitosan derivatives as effective antimicrobial agents for surface treatments and medical device coatings, particularly in applications where antibiotics are traditionally used, such as biofilm-prone environments.
    Keywords:   S. aureus ; AMR bacteria; Antimicrobial polymers; Bacterial biofilms; Growth inhibition
    DOI:  https://doi.org/10.1038/s41598-025-11891-1
  11. J Wound Care. 2025 Aug 02. 34(8): 564-570
    Wound dressings protect against bacterial environment: results of a prospective clinical study.
    Maurice Moelleken, Sebastian Heinrich Krimphove, Frederik Krefting, Christos Rammos, Anna Ewa Cyrek, Sven Benson, Joachim Dissemond.
       OBJECTIVE: Numerous bacteria are found in almost all wounds. Multidrug-resistant bacteria are a particular challenge. Wound dressings are primarily intended to improve wound healing. Their protective function for the environment and other people from the potentially pathogenic bacteria has been little studied. The aim of this cross-sectional study was to investigate the effectiveness of wound dressings in protecting the environment from bacterial contamination in a prospective clinical study within routine care.
    METHOD: Patients with wounds of different types were studied in an interdisciplinary certified wound care centre. Examinations were performed during routine patient visits. Wound-related data were collected and fluorescence images of all wounds, wound dressings and wound exteriors were taken.
    RESULTS: Of the 151 patients included, 68 (45%) were male and 83 (55%) were female. The wound duration ranged from 1-1399 weeks, with 77.5% being hard-to-heal (chronic) wounds. Wound care was provided by an ambulatory care service for 75 (49.7%) patients and by the patients themselves in 76 (50.3%) cases. A total of 67 (44.4%) patients used antimicrobial wound therapy. Using fluorescence photography, bacterial colonisation could be detected in 62 (41.1%) wounds; on the inner side of the wound dressings it was detectable in 19 (13.1%) and on the outside only in one wound dressing which had been incorrectly applied.
    CONCLUSION: In this study, both antimicrobial and non-antimicrobial dressings were shown to provide an effective barrier to bacterial penetration through the dressings when applied correctly. This ensured adequate protection of the environment and others from bacterial contamination when modern dressings were used correctly.
    Keywords:  antimicrobial; bacteria; chronic; colonisation; contamination; fluorescence; hard-to-heal; multidrug resistance; wound; wound care; wound dressing; wound healing
    DOI:  https://doi.org/10.12968/jowc.2024.0043
  12. J Wound Care. 2025 Aug 02. 34(8): 542-554
    Treatment of chronic wounds with cold plasma: a randomised, single-blind, placebo-controlled clinical study.
    Robert Strohal, Martina Mittlböck, Lisa Gebhardt, Gilbert Hämmerle.
       OBJECTIVE: This study aimed to investigate the wound healing properties of cold atmospheric plasma (CAP) in patients with chronic wounds.
    METHOD: This was a prospective, multicentre, two-arm, randomised, single-blind clinical study which compared the wound healing treatment of CAP with placebo, both of which were combined with best practice wound care.
    RESULTS: The study cohort consisted of 70 patients: 35 in the CAP group and 35 in the placebo group. There was a statistically significant (p<0.0001) reduction in the wound area at the end of the study, and faster wound healing, with the use of CAP compared with a placebo device.
    CONCLUSION: The results of this study showed that without requiring adjunctive therapies, the CAP device represents a safe, well-tolerated, and highly effective therapeutic option for wounds in that it promotes their rapid healing.
    Keywords:  chronic wounds; cold atmospheric plasma; placebo; plasma care; plasma device; wound; wound care; wound dressing; wound healing
    DOI:  https://doi.org/10.12968/jowc.2025.0207
  13. Diagnostics (Basel). 2025 Aug 01. pii: 1939. [Epub ahead of print]15(15):
    Clinical Relevance of PCR Versus Culture in Urinary Tract Infections Diagnosis: Quantification Cycle as a Predictor of Bacterial Load.
    Pallavi Upadhyay, Arjuna Vallabhaneni, Edward Ager, Barbara Alexander, Adriana Rosato, Vijay Singh.
      Background: Unambiguous clinical interpretation of PCR results for urinary tract infections (UTIs) remains a challenge. Here we compare and correlate multiplex qPCR results (quantification cycle values) with traditional microbial culture results (colony forming units) for clinical samples. Methods: Serial dilutions [108 to 100 colony forming units (CFU)/mL] were performed on five Gram-negative and two Gram-positive UTI-causing bacterial pathogens. For each dilution, quantitative cultures on solid media to confirm CFU/mL values and a real-time PCR UTI panel employing a nanofluidic Open ArrayTM platform producing quantification cycle (Cq) values were performed. Cq values were correlated with CFU/mL values, generating a semi-quantitative interpretive scale for clinical samples. The clinical utility of the scale was then assessed using PCR and culture data from 168 clinical urine samples. Results: For Gram-negative bacteria, Cq values of <23, 23 to 28, and >28 corresponded with ≥105 CFU/mL, <105 CFU/mL and negative cultures, respectively. For Gram-positive bacteria, Cq values of <26, 26 to 30, and >30 corresponded with ≥105 CFU/mL, <105 CFU/mL and negative cultures, respectively. Among 168 urine specimens (including 138 Gram-negative and 30 Gram-positive bacteria), there was 83.3% agreement (n = 140/168) and 16.6% non-agreement (n = 28/168) between culture CFU/mL and qPCR Cq. Gram-negative bacteria had higher agreement (87.6%, 121/138) than Gram-positive bacteria (63.3%, 19/30). Conclusions: This study demonstrates that qPCR Cq results can be directly correlated with traditional urine quantitative culture results and reliably identify the clinically relevant cutoff of 105 CFU/mL for detected uropathogens.
    Keywords:  colony forming units; multiplex PCR syndromic panel testing; quantification cycle; urinary tract infections; urine culture
    DOI:  https://doi.org/10.3390/diagnostics15151939
This page is being maintained by Thomas Krichel. It was last updated on 2025‒08‒17 at 13:58.