bims-fagtap 2025-08-10 papers

bims-fagtap

Biomed News

on Phage therapies and applications

Issue of 2025–08–10
fourteen papers selected by
Luca Bolliger, lxBio

[The Need for Phage Therapy in Combating Antimicrobial Resistance].
The potential of bacteriophages in treating multidrug-resistant ESKAPE pathogen infections.
The effect of bacteriophage in oral health: developing microbial ecology and emerging potential therapeutic target.
The importance of patient information and informed consent for unlicensed phage therapy.
Phage and enzyme therapies in wound infections: From lab to bedside.
An update on experimental to large-scale production of bacteriophages against superbugs: a review.
Long-term Storage Stability of Inhalable Phage Powder Formulations: A Four-Year Study.
Carbohydrates in action: influencing infection and amplification of Staphylococcus aureus bacteriophages.
Human bladder organoids model urinary tract infection and bacteriophage therapy.
Dual Antibiotics-Based pH-Responsive Carrier-Free Nanodrug against Bacterial Mixed Infection for Accelerated Wound Healing.
The current landscape of fecal microbiota transplantation in treating inflammatory bowel disease.
Cedecea infections in humans - A narrative review.
Emerging polymeric nanocarriers for mRNA and protein therapeutics: design, challenges, and clinical outlook.
The gut microbiota in cancer immunity and immunotherapy.

Yakugaku Zasshi. 2025 ;145(8): 679-688

[The Need for Phage Therapy in Combating Antimicrobial Resistance].

Kotaro Kiga.

  The escalating crisis of antimicrobial resistance poses a grave threat to global health and medicine in the 21st century. Phage therapy has emerged as a promising alternative to conventional antibiotics in addressing this urgent issue. Phages, unlike traditional antibiotics, leave the healthy microbiome largely undisturbed by selectively targeting and infecting their bacterial host. Additionally, phages can be readily genetically engineered to enhance their efficacy against specific bacterial strains. While some countries are slowly developing new regulations and implementing phage therapy in the clinic, widespread societal adoption remains limited. Phage therapy has the potential to revolutionize infection treatment; however, the unique biological properties of phages necessitate a multifaceted approach for the societal implementation of phage therapy. Recent research has focused on genetically engineering phages to enhance their capabilities or confer novel functions. Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems have facilitated the development of phages that target specific genes. Furthermore, the emergence of tRNA-carrying phages and phages that inhibit bacterial defense systems represents new classes of genetically engineered phages with enhanced bactericidal properties.

Keywords:  antimicrobial resistance; defense system; phage engineering; phage therapy; tRNA

DOI:  https://doi.org/10.1248/yakushi.24-00190-4
Expert Opin Ther Pat. 2025 Aug 08.

The potential of bacteriophages in treating multidrug-resistant ESKAPE pathogen infections.

Izadora Dillis Faccin, Gleyce Hellen de Almeida de Souza, Jean Carlos Pael Vicente, Nathalia da Silva Damaceno, Emily Vitória de Oliveira Perez, Willames Martins, Ana Cristina Gales, Simone Simionatto.

   INTRODUCTION: Antimicrobial resistance (AMR) and the emergence of multidrug-resistant bacteria, including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. (ESKAPE) pathogens, have significantly reduced the effectiveness of antibiotics. In this context, bacteriophage therapy offers a promising alternative, targeting specific bacterial strains, disrupting biofilms, minimizing side effects, and preserve beneficial microbiota.
AREAS RECOVERED: This review focuses on patent applications and patents granted up to 18 October 2024, related to the application of bacteriophages or their derivatives in treating infections caused by ESKAPE pathogens, as well as the methods for selecting bacteriophages.
EXPERT OPINION: Phage-based strategies to overcome AMR have piqued the interest of the scientific community owing to the limited efficacy of new antimicrobial agents. Bacteriophages, co-evolved with antimicrobial-resistant bacteria, offer a diverse and cost-effective arsenal, especially beneficial for low- to middle-income countries. This review examines various patents on phage applications, including those on computational methods used for improving phage cocktail design, classical phages or phage-derived proteins, and potential combinations of antimicrobial agents and phages. The increasing number of phage-related patents, especially in China and the United States, suggests that the antimicrobial activity of bacteriophages is a research hotspot.

Keywords:  Antimicrobial resistance; alternative therapy; bacterial viruses; novel antimicrobials; phage particles; phage therapy; therapeutic strategies

DOI:  https://doi.org/10.1080/13543776.2025.2545784
Future Microbiol. 2025 Aug 08. 1-10

The effect of bacteriophage in oral health: developing microbial ecology and emerging potential therapeutic target.

Mahsa Jalili, Farzad Mazloomirad, Farid Azizi Jalilian.

  The human oral cavity provides a convenient entry point for viruses and bacteria from the environment. The role of these viral communities remains unclear; however, many of them are bacteriophages that may actively influence the ecology of bacterial communities within the oral cavity. Bacteriophages are abundant and influential components of the oral microbiome and play a crucial role in shaping microbial ecology in oral health. They dynamically interact with oral bacteria, influencing biofilm formation, bacterial population structure, antibiotic resistance, and metabolic functions, thereby affecting disease progression and microbial community dynamics. Recent advances in studies have increased our understanding of oral phages and their impact on the amelioration of oral diseases such as periodontal disease. Nowadays, phage therapy has been identified as a potential therapeutic approach for major oral pathogens. The advantages of phage therapy include low toxicity, high specificity, the ability to penetrate biofilm structures, and the ability to replicate continuously in pathogenic bacteria. Hence, the aim of this review is to provide a comprehensive study about the role of bacteriophages as potential therapeutic target in oral health. Additionally, further studies are necessary to evaluate the role of phages in oral health and to develop safe and effective clinical applications in dentistry.

Keywords:  Bacteriophage; mouth diseases; oral health; oral microbiome; periodontal diseases; phage therapy

DOI:  https://doi.org/10.1080/17460913.2025.2535901
Clin Microbiol Infect. 2025 Aug 06. pii: S1198-743X(25)00373-8. [Epub ahead of print]

The importance of patient information and informed consent for unlicensed phage therapy.

Joshua D Jones, Helen J Stacey, Mehrunisha Suleman, Ross J Langley.



Keywords:  Bacteriophage; informed consent; patient information; phage therapy

DOI:  https://doi.org/10.1016/j.cmi.2025.07.032
Chin Med J (Engl). 2025 Aug 04.

Phage and enzyme therapies in wound infections: From lab to bedside.

Pan Yang, Jing Li, Zhangyong Song, Bin Chen, Shizhu Li.

   ABSTRACT: Antibiotic-resistant (AR) bacterial wound infections (WIs) impose major burdens on healthcare systems, exacerbated by ineffective therapies and stalled antibiotic development. Phage therapy and phage-derived enzymes have gained traction as potent alternatives, leveraging targeted bactericidal mechanisms to combat AR pathogens. In this review, we summarised the antimicrobial mechanisms of both phage therapy and phage-derived enzymes as antimicrobial therapy, and outlined recent advances in their use for in vitro, in vivo and clinical applications for WI management. In addition, we also highlights recent advancements in their development, driven by genetic engineering, chemical modifications, and artificial intelligence. Finally, we identified the potential barriers and challenges they may encounter in clinical practice and the corresponding strategies to address these issues. The entire review gives us a comprehensive understanding of the latest advances in phages and their derivative enzyme therapies for treating WIs, in the hope that research in this field will continue to improve and innovate, accelerating the transition from the laboratory to application at the bedside and ultimately improving the efficacy of treatment for AR bacterial WIs.

Keywords:  Antibiotic-resistance; Bacteria; Enzymes; Infection; Phage; Wound

DOI:  https://doi.org/10.1097/CM9.0000000000003626
Crit Rev Biotechnol. 2025 Aug 04. 1-20

An update on experimental to large-scale production of bacteriophages against superbugs: a review.

Mohammadreza Rahimian, Elham Mohammadi, Mohammad Aghazadeh-Soltan-Ahmadi, Alireza Samari, Nosratollah Zarghami.

  The escalating problem of antibiotic resistance has sparked renewed interest in bacteriophages (phages) as potential substitutes for conventional antibiotics in treating infectious diseases, improving food safety, and advancing sustainable agriculture. The key phage research processes, such as host range, burst size, and environmental stability tests, strongly influence phage production processes. Hence, the standardization of the mentioned techniques must be prioritized. The introduction of high-throughput sequencing technologies with high accuracy and the emergence of novel bioinformatic tools to analyze the resulting raw molecular data provide comprehensive identification of phages and phage-verse (the universe of phage). While encapsulation of phages was studied comprehensively before, the production of encapsulated phages is still unclear. Moreover, recent advances in artificial intelligence (AI) contribute to phage research by increasing the accuracy of bioinformatic tools, improving resistance profiling, and facilitating phage host prediction. Incorporating AI promises a future of automated, precisely tailored phage applications. This review covers efficient techniques appropriate for industrial and agricultural applications as well as large-scale phage production methods, covering upstream and downstream processing. Also, encapsulated phage production and AI-based automated systems in various applications are proposed in this review. By covering both present issues and potential future uses of phages in the fight against antibiotic resistance, this review seeks to give academics and industry experts the fundamental information they need to advance phage-based solutions.

Keywords:  AI; AMR; Bacteriophage; biocontrol; encapsulation; phage manufacturing; scale-up

DOI:  https://doi.org/10.1080/07388551.2025.2531446
AAPS J. 2025 Aug 04. 27(5): 128

Long-term Storage Stability of Inhalable Phage Powder Formulations: A Four-Year Study.

Mengyu Li, Wei-Ren Ke, Rachel Yoon Kyung Chang, Hak-Kim Chan.

  The growing potential of bacteriophage therapy as an alternative treatment for pulmonary infections caused by multidrug-resistant bacteria has been increasingly recognized. This study aimed to evaluate the long-term stability of spray-dried phage powder formulations for pulmonary delivery, focusing on both biological activity and physicochemical properties. Three phages, PEV1, PEV20, and PEV61, were selected for formulation based on their host range against clinical strains of Pseudomonas aeruginosa. Eight spray-dried formulations, developed with varying proportions of lactose as a stabilizer and leucine as a moisture protectant and powder dispersion enhancer, were stored under controlled conditions at 4°C/15% relative humidity (RH) and 20°C/15% RH for four years. Over this period, phage titers declined with reduction ranging from 0.97 log10 in the most stable formulation to 2.49 log10 in the least stable one. Formulations with higher lactose concentrations (70-80%) demonstrated better preservation of biological activity. While the overall particle morphology remained unchanged, some thread-like elongated features protruding from the particle surfaces were observed, particularly in powders stored at 20°C/15% RH. However, there was a decline in the fine particle fraction (FPF) 50 - 60% to 27-44%. These findings showed the potential of spray-dried phage powders as a viable option for long-term storage to retain bioactivity, but the aerosol performance can be compromised.

Keywords:  bacteriophage; formulation; powder inhalation; pulmonary delivery; spray drying; stability

DOI:  https://doi.org/10.1208/s12248-025-01112-y
BMC Microbiol. 2025 Aug 05. 25(1): 483

Carbohydrates in action: influencing infection and amplification of Staphylococcus aureus bacteriophages.

Poniatovskyi Vadym, Shyrobokov Volodymyr.

   BACKGROUND: The use of bacteriophages as adjunct antibacterial agents in combating antimicrobial resistance is being actively studied worldwide. Due to their high specificity and ability to replicate within bacterial hosts, phages are used in various fields, including medicine, the food industry, agriculture, animal husbandry, biotechnology, and microbial identification. Despite their exceptional properties, the self-replication process of phages depends on multiple factors that may lead to a decrease in phage concentration during production and storage. The composition of the culture medium used for the cultivation of host bacteria is one of the critical parameters affecting phage infection and replication processes.
RESULTS: In this study, we evaluated the effect of different carbohydrates in the nutrient medium on the infection and amplification of bacteriophages in a Staphylococcus aureus bacterial culture. We used the bacteriophage St12f, isolated from environmental samples, and tested 21 carbohydrates and their derivatives. The experimental results confirmed that the addition of carbohydrates to nutrient media either inhibited or enhanced the plaque formation. The addition of 1% inositol (P ≥ 0.05) and maltose (P < 0.05) to the nutrient medium enhanced plaque formation by the St12f phage, whereas sucrose, lactose, mannitol, sorbitol, glycerol, rhamnose, xylose, arabinose, and glucose (P < 0.05) at the same concentration significantly inhibited the formation of phage plaques. Furthermore, we identified a dependence of phage replication (inhibition/enhancement) on the carbohydrate concentration in the medium.
CONCLUSIONS: The experimental data obtained contribute to a deeper understanding of the metabolic interactions between bacteriophages and their bacterial hosts, as well as to the optimization of phage production for therapeutic applications. Further research should focus on elucidating the molecular mechanisms underlying this phenomenon and assessing its clinical significance.

Keywords:   Staphylococcus aureus ; Bacteriophages; Carbohydrates; Infection cycle; Plaque formation

DOI:  https://doi.org/10.1186/s12866-025-04219-6
bioRxiv. 2025 Jul 30. pii: 2025.07.30.667685. [Epub ahead of print]

Human bladder organoids model urinary tract infection and bacteriophage therapy.

Jacob J Zulk, Clare M Robertson, Samantha Ottinger, Amal Kambal, Alejandra Rivera Tostado, Rachel C Fleck, Allyson E Shea, Cristian Coarfa, Sarah E Blutt, Anthony W Maresso, Kathryn A Patras.

Urinary tract infections (UTIs), primarily caused by uropathogenic Escherichia coli (UPEC), are among the most common antibiotic-resistant infections. Despite this, currently available preclinical UTI models lack the breadth of morphotypic and heterogenous cell populations of the human bladder, impairing the development of novel therapies. To address these limitations, we developed human bladder organoids derived from the bladder stem cells of multiple healthy donors which recapitulate cellular diversity of the urothelium. Using bulk and single cell RNA-sequencing, we characterized organoid responses to UPEC and phage exposure individually and in combination to model phage therapy. Although phage minimally affected the uroepithelium in the absence of infection, during UTI, phage treatment reduced bacterial burdens and dampened inflammatory responses and barrier disruption. Collectively, our findings highlight human bladder organoids as a tool for capturing conserved and individual-specific uroepithelial responses to infection while also providing preclinical efficacy and safety testing for therapeutic development.

DOI: https://doi.org/10.1101/2025.07.30.667685
Adv Healthc Mater. 2025 Aug 05. e01845

Dual Antibiotics-Based pH-Responsive Carrier-Free Nanodrug against Bacterial Mixed Infection for Accelerated Wound Healing.

Jiali Yang, Xiaoyu Zhang, Yanan Fu, Guofeng Li, Wensheng Xie, Xing Wang.

  Mixed infections caused by multiple bacteria are a key challenge hindering wound healing in the field of trauma care. Although antibiotics have exhibited efficient therapeutic efficacy, it is difficult for a single antibiotic to exert synergistic bactericidal effects against both Gram-positive (G⁺) and Gram-negative (G-) bacteria in mixed infection. Meanwhile, long-term treatment in high doses is prone to induce drug toxicity and accelerate the emergence of drug-resistance. Therefore, in this study, polymyxin B (PMB, targeting G- bacteria) and bornyl p-aldehyde benzoate (BF, targeting G⁺ bacteria) are introduced to construct pH-responsive carrier-free nanodrug (PBN) via a molecular self-assembly strategy based on dynamic Schiff-base bonding. Once triggered by the acidic microenvironment in infection site, PBN can specifically release PMB and BF synchronously through Schiff-base bond breaking, which then targeting and killing multidrug-resistant Pseudomonas aeruginosa (MDR-PA) and Staphylococcus aureus (MDR-SA), respectively. Compared with PMB/BF dual-drug administration, PBN presents higher efficiency for disrupting the membrane integrity of mixed infection. Furthermore, in vivo experiments confirm that PBNs can efficiently eliminate bacterial mixed infection to accelerate wound healing. Considering the good biosafety, the carrier-free self-assemble strategy based on different antibiotics provides an innovative route for the treatment of bacterial mixed infections.

Keywords:  Gram‐negative bacteria; Gram‐positive bacteria; bacterial mixed infection; carrier‐free nanodrug; synergistic antibacterial

DOI:  https://doi.org/10.1002/adhm.202501845
Transl Gastroenterol Hepatol. 2025 ;10 55

The current landscape of fecal microbiota transplantation in treating inflammatory bowel disease.

Yajun Bi, Bomin Cheng, Biao Zou, Shengxuan Liu, Zhenze Cui.

  Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is a chronic, immune-mediated disorder that impacts the intestinal tract. The gut microbiota, a diverse community of microorganisms, plays a pivotal role in the initiation, development, and progression of IBD by modulating inflammation, and immune responses, and maintaining gut homeostasis. Dysbiosis, or an imbalance in the gut microbiota, is frequently observed in IBD patients and is believed to contribute to the pathogenesis of the disease by disrupting the mucosal immune system. Fecal microbiota transplantation (FMT) involves transferring feces from a healthy donor (HD) into a recipient and has emerged as a promising therapeutic approach for IBD. The primary goal of FMT is to restore microbial balance in the recipient's gut, improving both microbiota composition and immune function. Numerous preclinical and clinical studies have demonstrated varying degrees of success in alleviating IBD symptoms through FMT. The benefits of FMT include modulation of gut bacteria abundance, restoration of microbial diversity, and enhancement of immune system regulation, all of which contribute to reducing IBD-related inflammation. This review presents a comprehensive analysis of animal studies and clinical trials exploring using FMT as a treatment for IBD. Understanding the underlying mechanisms of FMT in IBD is crucial for designing effective therapeutic strategies and optimizing its clinical impact.

Keywords:  Crohn’s disease (CD); Inflammatory bowel disease (IBD); fecal microbiota transplantation (FMT); inflammation; ulcerative colitis (UC)

DOI:  https://doi.org/10.21037/tgh-24-138
Diagn Microbiol Infect Dis. 2025 Jul 25. pii: S0732-8893(25)00349-9. [Epub ahead of print]113(4): 117026

Cedecea infections in humans - A narrative review.

Sofia Maraki, Viktoria Eirini Mavromanolaki, Evangelia Iliaki-Giannakoudaki, Anna Kasimati.

   BACKGROUND: Cedecea species are Gram-negative, facultative anaerobic, non-sporulating, catalase-positive, oxidase-negative and motile rod shaped bacteria belonging to Enterobacteriaceae family. Members of the genus Cedecea are rarely reported to cause human infections. These infections primarily occur in immunocompromised patients with severe underlying medical conditions. The objective of this review was to collect and evaluate all published documented cases of Cedecea spp. human infections.
METHODS: We searched PubMed and Scopus databases for articles providing data related to the epidemiology, clinical features and microbiology of Cedecea human infections.
RESULTS: A total of 49 studies involving 50 patients with Cedecea infections were regarded as eligible for inclusion in our review. The mean patient age was 53.3 years and most (72 %) were male. Comorbidities were common in 88 % of the patients. The most common types of infection were bacteremia, respiratory tract infections, soft tissue infections and urinary tract infections, and more than half of them were healthcare-associated. C. lapagei was the predominant species, followed by C. davisae and C. neteri. High rates of resistance were recorded for ampicillin (47.6 %), gentamicin (38.1 %), amoxicillin-clavulanate, cephalothin, and ceftazidime (33.3 %) each. Ciprofloxacin was the most frequently used antibiotic, followed by meropenem. The median treatment duration was 14 days. The outcome was favorable for the majority of the patients (87.8 %). The mortality rate attributed to the infection was 10.2 %.
CONCLUSIONS: Physicians should be aware of this rare pathogen that exhibits resistance to many antibiotics, so they can tailor antimicrobial treatment based on susceptibility testing results to optimize outcome.

Keywords:  Antimicrobial resistance; Bacteremia; Cedecea species; Infections; Respiratory tract infections

DOI:  https://doi.org/10.1016/j.diagmicrobio.2025.117026
Nanomedicine (Lond). 2025 Aug 05. 1-18

Emerging polymeric nanocarriers for mRNA and protein therapeutics: design, challenges, and clinical outlook.

Chloe Forenzo, Noah Arnold, Jessica Larsen.

  As the healthcare landscape rapidly evolves to include advanced drug delivery methods with better cellular targeting and more efficient delivery, polymeric nanocarriers have emerged to close translational gaps. Acting on the central dogma of molecular biology, mRNA and protein therapeutics can offer curative potential for various debilitating diseases. Considering these advancements, polymeric nanocarriers have been widely explored preclinically in delivering both proteins and mRNA for various disease therapies. This review introduces how the next generation of polymeric nanocarriers can be designed for protein therapeutics, including some advantages and disadvantages as well as specific design considerations for mRNA vs protein delivery. The evolution of these polymeric nanocarriers is then examined, and the current landscape and emerging trends are presented. Finally, we provide an outlook on the clinical translation of polymeric nanocarrier delivery of mRNA and proteins, including a future perspective for the field. Despite the preclinical promise of these delivery systems in both mRNA and protein constructs, clinical translation is underwhelming. Continued development of polymeric nanocarriers is underway and early clinical trials have provided a foothold into translation for this technology. A key challenge for polymeric nanomedicine is bridging the gap between promising preclinical data and successful clinical translation.

Keywords:  Polymeric nanocarriers; biodegradable polymers; biological drug delivery; clinical translation; controlled release; intracellular delivery; mRNA delivery; protein therapeutics

DOI:  https://doi.org/10.1080/17435889.2025.2542110
Cell Mol Immunol. 2025 Aug 06.

The gut microbiota in cancer immunity and immunotherapy.

Mingxu Xie, Xiang Li, Harry Cheuk-Hay Lau, Jun Yu.

  The human gastrointestinal tract harbors trillions of microorganisms, including bacteria, fungi, and viruses, to form the gut microbiota. Cumulative evidence has demonstrated the critical impact of gut microbes on cancer immunity. In cancer, an altered gut microbiota enriched with pathogenic bacteria can actively promote immune evasion and disrupt antitumor immunity, thereby supporting tumor growth and survival. Conversely, beneficial commensal bacteria (e.g., Lactobacillus and Bifidobacterium) have emerged as therapeutic probiotics for cancer prevention and as adjuvants for cancer therapy. The gut microbiota is also closely linked to the efficacy of immunotherapy. This review summarizes the effects of pathogenic bacteria and beneficial commensals, including T cells, B cells, natural killer cells, innate lymphoid cells, and myeloid-derived suppress cells, on various innate and adaptive immune cell populations in cancer. It also explores the mechanisms by which the gut microbiota influences immunotherapy efficacy, such as the modulation of innate immune cells and CD8+ T cells. Given its importance, an increasing number of studies have developed approaches to target the gut microbiota to improve immunotherapy outcomes and reduce immune-related adverse events. These strategies include antimicrobial intervention, probiotics, prebiotics/dietary modifications, microbial metabolites, phage therapy, and fecal microbiota transplantation. This review also evaluates clinical applications that use the gut microbiota to predict immunotherapy outcomes. Overall, the current understanding of host‒microbe interactions within the tumor microenvironment has laid a critical foundation for the translation of microbiota research into clinical practice, ultimately benefiting patients.

Keywords:  Cancer immunity; Gut microbiota; Immunotherapy response; Microbial modulation strategies; Tumor microenvironment

DOI:  https://doi.org/10.1038/s41423-025-01326-2