bims-fagtap 2025-05-04 papers

bims-fagtap

Biomed News

on Phage therapies and applications

Issue of 2025–05–04
27 papers selected by
Luca Bolliger, lxBio

[Potential of bacteriophage therapy in Germany: evidence and clinical relevance].
Harnessing the Activity of Lytic Bacteriophages to Foster the Sustainable Development Goals and the "One Health" Strategy.
Isolation and characterization of a novel bacteriophage ST1749 and its effectiveness against Vibrio parahaemolyticus and Salmonella spp.
Antimicrobial potential of a novel K5-specific phage and its recombinant strains against Klebsiella pneumoniae in milk.
[Basic knowledge of phages and their therapeutic application].
Impact of prophages on gut microbiota and disease associations.
The joint action of antibiotics, bacteriophage, and the innate immune response in the treatment of bacterial infections.
Development of Inhalable Bacteriophage Liposomes Against Pseudomonas aeruginosa.
Abundance measurements reveal the balance between lysis and lysogeny in the human gut microbiome.
Telomere bacteriophages are widespread and equip their bacterial hosts with potent interbacterial weapons.
Phage-Based Control of Listeria innocua in the Food Industry: A Strategy for Preventing Listeria monocytogenes Persistence in Biofilms.
Personalized inhaled bacteriophage therapy for treatment of multidrug-resistant Pseudomonas aeruginosa in cystic fibrosis.
Inflammation, toxicity, and apoptosis reducing potential of bacteriophage Ariobarzanes on intestinal cells infected with Salmonella Typhimurium.
A bacteriophage-conditional mouse model reveals the impact of phages within a conventionally colonized gut microbiota.
Identification of a broad-spectrum lytic Bordetella phage and assessments of its potential for combating Bordetella infections.
Genome sequences of two phages active against cystic fibrosis isolates of Pseudomonas aeruginosa.
Gut-directed therapeutics in inflammatory bowel disease.
Sequestering survival: sponge-like proteins in phage evasion of bacterial immune defenses.
Exogenous hydrogen sulfide sensitizes carbapenemase-producing Acinetobacter baumannii to gentamicin.
How to fix a gut microbiome ravaged by antibiotics.
Key Insights into Gut Alterations in Metabolic Syndrome.
Staphylococcus aureus Biofilm-Associated Infections: Have We Found a Clinically Relevant Target?
The Discovery of Phages in the Substantia Nigra and Its Implication for Parkinson's Disease.
Bacteriophage therapy in women with chronic recurrent cystitis caused by multidrug-resistant bacteria: A prospective, observational, comparative study.
New Therapeutic Challenges in Pediatric Gastroenterology: A Narrative Review.
Phage/aptamer dual-encoded hydrogel arrays integrated with microfluidic platforms for simultaneous detection of multiple food pathogens.
Exploring and Evaluating Microbiome Resilience in the Gut.

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2025 Apr 28.

[Potential of bacteriophage therapy in Germany: evidence and clinical relevance].

Felix Bröcker, Christian Willy.

  Bacteriophage therapy (phage therapy) holds great potential in addressing the growing threat of infections caused by multidrug-resistant bacteria. Registry studies and systematic reviews indicate that phage treatments are effective in approximately 80-90% of antibiotic-resistant infections across various indications. In principle, the approximately 62,000 annual cases of infections caused by resistant or difficult-to-treat pathogens in Germany could be treated with phage therapy. Currently, several clinical trials are underway to assess the safety and efficacy of phage therapy for specific indications; however, no product has yet undergone a formal approval process. Furthermore, the timely applicability of phage therapy for individual cases is constrained by high production costs, limited capacities, and regulatory hurdles. The first market approvals in the USA and Europe are expected within the next three to five years, which could significantly strengthen the outlook for phage therapy. Concrete steps to accelerate the implementation of phage therapy in Germany to relieve the healthcare system include establishing a dedicated phage manufacturing facility, reducing regulatory barriers for compassionate use, promoting innovative technologies for production and diagnostics, and supporting clinical approval studies.

Keywords:  Antibiotic resistance; Case studies; Clinical trials; Multidrug resistance; Phage therapy

DOI:  https://doi.org/10.1007/s00103-025-04048-y
Viruses. 2025 Apr 09. pii: 549. [Epub ahead of print]17(4):

Harnessing the Activity of Lytic Bacteriophages to Foster the Sustainable Development Goals and the "One Health" Strategy.

Belén Álvarez, Elena G Biosca.

  As bacteriophages (phages) are viruses that infect and destroy bacterial cells, they can be considered natural bactericides that can either directly or indirectly contribute to the achievement of the United Nations Sustainable Development Goals (UN SDGs) on health and well-being, food production and food security, as well as environmental protection and climate change mitigation, thus contributing to the success of the European "One Health" strategy to combat antimicrobial resistance in humans, animals, plants, and the environment. The biological activity of lytic bacteriophages can operate in the fields of microbiology and biotechnology for clinical, veterinary, agricultural, and industrial applications, among others, to achieve the proposed goals, mainly because the phages can help increase crop productivity by reducing bacterial diseases; constitute alternative therapies against infections caused by multidrug-resistant bacteria; can reduce populations of pathogenic bacteria that contaminate soil and water, therefore ensuring healthier and safer food production; and they can help reduce environmental pollution caused by the presence of agrochemicals and antibiotics. Phage-based therapies developed through research and innovation have the potential to promote greater global food security and health in a more environmentally friendly and eco-sustainable way.

Keywords:  SDGs; agrochemical; antibiotic; biological control; biotechnological application; global health; phage; phage therapy; resistant bacteria; virus

DOI:  https://doi.org/10.3390/v17040549
Virus Res. 2025 Apr 27. pii: S0168-1702(25)00056-5. [Epub ahead of print] 199579

Isolation and characterization of a novel bacteriophage ST1749 and its effectiveness against Vibrio parahaemolyticus and Salmonella spp.

Truong Thi Bich Van, Nguyen Thi Loan Anh, Van-Thanh Vo, Nguyen Pham Anh Thi.

  Bacteriophages are extensively employed across various fields, including medicine, veterinary medicine, the food industry, agriculture, biotechnology, and pharmacy, owing to their numerous advantages. These advantages include rapid clearance of pathogens, self-propagation at the infection site, host specificity, potential for genetic modification, ease of isolation, stability, and low production costs. This study isolated a bacteriophage from shrimp pond wastewater in the Mekong Delta region. The bacteriophage was identified as a lytic bacteriophage belonging to the genus Bruyoghevirus, class Caudoviricetes, with the ability to effectively lyse three bacterial strains: V. parahaemolyticus, S. enteritidis, and S. typhimurium. Growth curve analysis revealed variations in the latency period and the number of phages produced during the life cycle across all three hosts. Bacteriophage Produced 117, 176, and 52 PFU/cell against V. parahaemolyticus, S. enteritidis, and S. typhimurium, respectively. Phage ST1749 demonstrated activity across a broad range of temperatures (-20°C to 70°C) and pH levels (2 to 10), with optimal stability observed at pH 5 to 7. Furthermore, phage ST1749 exhibited biofilm-degrading and lytic capabilities against the three bacterial strains studied. These findings suggest that phage ST1749 has the potential to serve as a biocontrol agent for treating infections caused by antibiotic-resistant bacteria.

Keywords:  Bacteriophage ST1749; Bruyoghevirus; Caudoviricetes; Vibrio parahaemolyticus; biocontrol; biofilm

DOI:  https://doi.org/10.1016/j.virusres.2025.199579
J Dairy Sci. 2025 Apr 28. pii: S0022-0302(25)00272-3. [Epub ahead of print]

Antimicrobial potential of a novel K5-specific phage and its recombinant strains against Klebsiella pneumoniae in milk.

Pei Li, Zhuojun Li, Wan Peng, Xiaoyue Li, Genglin Guo, Long Chen, Xiaoxiao Pang, Mianmian Chen, Juan Li, Yinglu Wei, Yishan Zheng, Wei Zhang.

  The nutrient-rich composition of milk creates an optimal environment for bacterial proliferation, making the inhibition of microbial growth essential for maintaining dairy product quality and ensuring consumer safety. Klebsiella pneumoniae is an important contaminant of milk and a leading cause of bovine mastitis. Although the increasingly serious antibiotic resistance has led to a renewed interest in phage therapy, research on antimicrobial potential of Klebsiella phages in milk remains scarce. The K5 serotype of K. pneumoniae is a major concern due to its high virulence and prevalence in dairy farming operations. Despite its clinical and economic importance, the availability of phages specifically targeting this serotype remains substantially limited. Here, we successfully isolated and sequenced 2 K1-specific Klebsiella phages, P284 and P287, and one K5-specific Klebsiella phage P252. We identified the receptor-binding proteins with depolymerization activity in these phages. The phage library against K5 K. pneumoniae was enriched by phage genome modification. Specifically, we replaced the receptor-binding protein of K1-specific phage P284 with that of K5-specific phage P252, resulting in the generation of recombinant phages T and F, which exhibit specific lytic activity against K5 K. pneumoniae. Compared with phage P252, recombinant phages T and F exhibited better and more prolonged antibacterial potential in planktonic assay. In addition, all these K5-specific phages could significantly inhibit bacterial growth and reduce bacterial populations in milk at 4°C and 38°C. In summary, this study provided K5-specific phages with potential application in managing K. pneumoniae contamination and infection in the dairy industry.

Keywords:  K5; Klebsiella pneumoniae; milk; phage; receptor-binding protein

DOI:  https://doi.org/10.3168/jds.2024-25895
Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2025 May 02.

[Basic knowledge of phages and their therapeutic application].

Christine Rohde.

  Phages (bacteriophages) are viruses that specifically infect and kill bacteria. They are very abundant in nature, playing a highly relevant role in microbial ecosystems. In medicine, they are investigated as a potential alternative or supplement to antibiotics and can be used to treat wound, urinary tract and lung infections, for example. Single phages or so-called "phage cocktails" are applied.This overview article on basic knowledge of phages sheds light on well-known keywords from classical knowledge of phage biology and on state-of-the-art research focuses. Mechanisms of phage activity are presented as a basis for therapeutic application. Particularly, the phage-host interaction, lysis mechanisms, phage morphologies and specific methods for visualisation are discussed. Being part of the human microbiome, phages contribute to immune defence, especially in the mucosa. Temperate phages that are able to reside in bacterial genomes as prophages and therefore not suitable for therapy use as well as the CrAss phages (Crassvirales) and Lak megaphages discovered in recent years are also introduced. Further topics are bacterial phage defence, phage resistance and phage-antibiotic synergies. An outlook on future research is given, emphasising the importance of a coordinated collection of scientific results.Phages should not replace antibiotics, but they can even improve their efficiency. Currently, the licensing processes for phage therapy are still challenging. However, trust in phage preparations must be based on quality, which has to be guaranteed by harmonised standards.

Keywords:  Coevolution; Lytic cycle; Phage resistance; Phageome; Temperate phages

DOI:  https://doi.org/10.1007/s00103-025-04051-3
Microb Pathog. 2025 Apr 27. pii: S0882-4010(25)00367-5. [Epub ahead of print]204 107642

Impact of prophages on gut microbiota and disease associations.

Aminu Abdullahi Mahmoud, Xiaoyu Wang, Xinyu Liao, Song Zhang, Tian Ding, Juhee Ahn.

  The gut microbiota plays an important role in maintaining host health by affecting various physiological functions. Among the diverse microbial communities in the gut, prophages are integral components of bacterial genomes, contributing significantly to bacterial evolution, ecology and pathogenicity. Prophages are capable of switching to lytic cycles in response to various internal and external factors. Factors that induce prophage induction include DNA damage, oxidative stress, nutrient availability, host immune response, quorum sensing, diet, secondary metabolites, antibiotics, and lifestyle changes. Prophage induction could contribute to both gut homeostasis and dysbiosis. Importantly, the connections between prophage induction and disorders such as inflammatory bowel disease, ulcerative colitis, and bacterial vaginosis highlight the dual roles of prophages in both health and disease. Although therapeutic approaches such as phage therapy (PT), fecal microbiota transplants (FMT), and fecal virome transplants (FVT) have gained attention, the concept of dietary prophage induction therapy offers a novel, targeted method to modulate gut microbiota. In spite of recent advances in understanding the role of prophages in gut health, the exact mechanisms by which they influence gut health remain only partially understood. Therefore, further research is needed to elucidate additional molecular mechanisms of prophage induction pathways and to explore their implications for gut microbiota dynamics and disease associations. This review discusses the molecular mechanisms and key factors that trigger prophage induction in the gut. Insights into these processes could lead to innovative therapeutic strategies that utilize prophages to support gut health.

Keywords:  Gut health; Gut microbiota; Lytic cycle; Prophage induction; Therapeutic strategy

DOI:  https://doi.org/10.1016/j.micpath.2025.107642
bioRxiv. 2025 Apr 10. pii: 2025.04.10.648192. [Epub ahead of print]

The joint action of antibiotics, bacteriophage, and the innate immune response in the treatment of bacterial infections.

Brandon A Berryhill, Teresa Gil-Gil, Bruce R Levin.

Studies of antimicrobial therapeutics have traditionally neglected the contribution of the host in determining the course of treatment and its outcome. One critical host element, which shapes the dynamics of treatment is the innate immune system. Studies of chemotherapeutics and complementary therapies such as bacteriophage (phage), are commonly performed with mice that purposely have an ablated innate immune system. Here, we generate a mathematical and computer-simulation model of the joint action of antibiotics, phage, and phagocytes. Our analysis of this model highlights the need for future studies to consider the role of the innate immune system of a host in determining treatment outcomes. Critically, our model predicts that the conditions under which resistance to the treatment agent(s) will emerge are much narrower than commonly anticipate. We also generate a second model to predict the dynamics of treatment when multiple phages are used. This model provides support for the application of cocktails to treat infections rather than individual phages. Overall, this study provides hypotheses that can readily be tested experimentally with both in vitro and in vivo experiments.

DOI: https://doi.org/10.1101/2025.04.10.648192
Pharmaceutics. 2025 Mar 24. pii: 405. [Epub ahead of print]17(4):

Development of Inhalable Bacteriophage Liposomes Against Pseudomonas aeruginosa.

Shruti S Sawant, Maizbha Uddin Ahmed, Nathan-Gautham Gantala, Caitlin Chiu, Li Qu, Qi Zhou.

  Background:Pseudomonas aeruginosa is one of the major pathogens that cause respiratory infections. The rise of antimicrobial resistance has prompted a need for alternatives to conventional antibiotics. Bacteriophages (phages), natural predators of bacteria, are gaining interest as an alternative therapeutic option against drug-resistant infections. However, phage viability can be lost during manufacturing and delivery. Recent studies show that phages can be taken up by lung epithelial cells, which makes fewer phages available for antibacterial action against extracellular bacteria P. aeruginosa in the airways. Methods: In this study, we encapsulated phages in liposomes using thin film hydration. The effect of processing conditions and phage loading titer on the phage encapsulation and viability was studied. The impact of nebulization on phage viability was tested using an air-jet nebulizer (PARI-LC Plus). Phage cellular uptake was evaluated using an in vitro H441 lung epithelial cell model, grown at the air-liquid interface. Results: Our results demonstrate favorable encapsulation (58 ± 6.02%) can be achieved with minimum loss in phage titer (0.64 ± 0.21 log) by using a low phage titer for hydration. The liposomal formulations exhibited controlled release of phages over 10 h. The formulation also reduced the loss of phage viability during nebulization from 1.55 ± 0.04 log (for phage suspension) to 1.08 ± 0.05 log (for phage liposomes). Encapsulation of phages in liposomes enabled a two-fold reduction in phage cellular uptake and longer extracellular phage retention in the human lung epithelial cell monolayer. Conclusions: Our results indicate that liposomal encapsulation favors phage protection and improves phage availability for antibacterial activity. These findings highlight the potential of liposomes for inhaled phage delivery.

Keywords:  bacteria; inhalation; liposomes; nebulization; phages; pulmonary delivery

DOI:  https://doi.org/10.3390/pharmaceutics17040405
Curr Biol. 2025 Apr 26. pii: S0960-9822(25)00389-6. [Epub ahead of print]

Abundance measurements reveal the balance between lysis and lysogeny in the human gut microbiome.

Jamie Alcira Lopez, Saria McKeithen-Mead, Handuo Shi, Taylor H Nguyen, Kerwyn Casey Huang, Benjamin H Good.

  The human gut contains diverse communities of bacteriophage, whose interactions with the broader microbiome and potential roles in human health are only beginning to be uncovered. Here, we combine multiple types of data to quantitatively estimate gut phage population dynamics and lifestyle characteristics in human subjects. Unifying results from previous studies, we show that an average human gut contains a low ratio of phage particles to bacterial cells (∼1:100) but a much larger ratio of phage genomes to bacterial genomes (∼4:1), implying that most gut phage are effectively temperate (e.g., integrated prophage and phage-plasmids). By integrating imaging and sequencing data with a generalized model of temperate phage dynamics, we estimate that phage induction and lysis occur at a low average rate (∼0.001-0.01 per bacterium per day), imposing only a modest fitness burden on their bacterial hosts. Consistent with these estimates, we find that the phage composition of a diverse synthetic community in gnotobiotic mice can be quantitatively predicted from bacterial abundances alone while still exhibiting phage diversity comparable to native human microbiomes. These results provide a foundation for interpreting existing and future studies on links between the gut virome and human health.

Keywords:  bacteriophage; gut microbiome; induction; mathematical modeling; metagenomics; microbial ecology; population dynamics; virome; virus; virus-to-microbe ratio

DOI:  https://doi.org/10.1016/j.cub.2025.03.073
Sci Adv. 2025 May 02. 11(18): eadt1627

Telomere bacteriophages are widespread and equip their bacterial hosts with potent interbacterial weapons.

Sally M H Byers, Andrea Rocker, To N T Nguyen, Natalia C Rosas, George Taiaroa, Kher Shing Tan, Yan Li, Jonathan J Wilksch, Joel R Steele, Ralf B Schittenhelm, Rhys A Dunstan, Francesca L Short, Trevor Lithgow.

Bacteriophages (phages) are viruses that can kill bacteria, thereby editing and shaping microbial communities. The telomere phages are a curious form using telomere-like structures to replicate their genomes as linear extrachromosomal elements. Here, we find that telomere phages are widely distributed in bacteria, being highly prevalent in Klebsiella species. We establish a model system to investigate telomere phage biology by isolating the virions of telomere phages and infecting naïve strains to create isogenic lines with and without a phage. We find that only a small set of telomere phage proteins is expressed in phage-host cells, including a toxin-the telocin-that kills other Klebsiella strains. We identify and validate a set of telocins in the genomes of other prevalent Klebsiella telomere phages. Thus, telomere phages are widespread elements encoding diverse antibacterial weapons and we discuss the prospect of using telocins for precision editing of microbial populations.

DOI: https://doi.org/10.1126/sciadv.adt1627
Viruses. 2025 Mar 27. pii: 482. [Epub ahead of print]17(4):

Phage-Based Control of Listeria innocua in the Food Industry: A Strategy for Preventing Listeria monocytogenes Persistence in Biofilms.

Anna Zawiasa, Marcin Schmidt, Agnieszka Olejnik-Schmidt.

  Listeria innocua, though considered non-pathogenic, frequently coexists with Listeria monocytogenes in industrial environments, aiding its survival in biofilms. These biofilms pose a significant challenge in food processing facilities, as they protect bacteria from disinfectants and facilitate their spread. The aim of this review was to identify bacteriophages as a promising method for eliminating Listeria biofilms from the food industry. Lytic bacteriophages show great potential in combating Listeria biofilms. Commercially available products, such as PhageGuard Listex™ (P100) (Micreos Food Safety, Wageningen, The Netherlands), effectively reduce both L. monocytogenes and L. innocua in food products and on production surfaces. Additionally, phage-derived enzymes, such as endolysins, can degrade biofilms, eliminating bacteria without compromising food quality. The following article highlights that although bacteriophages present a promising biocontrol method, further research is necessary to assess their long-term effectiveness, particularly regarding bacterial resistance. To maximize efficacy, a combination of strategies such as phage cocktails and disinfectants is recommended to enhance biofilm eradication and minimize food contamination risks.

Keywords:  Listeria innocua; Listeria monocytogenes; bacteriophages; biofilms; safety

DOI:  https://doi.org/10.3390/v17040482
Nat Med. 2025 Apr 29.

Personalized inhaled bacteriophage therapy for treatment of multidrug-resistant Pseudomonas aeruginosa in cystic fibrosis.

Benjamin K Chan, Gail L Stanley, Kaitlyn E Kortright, Albert C Vill, Mrinalini Modak, Isabel M Ott, Ying Sun, Silvia Würstle, Casey N Grun, Barbara I Kazmierczak, Govindarajan Rajagopalan, Zachary M Harris, Clemente J Britto, Jill Stewart, Jaideep S Talwalkar, Casey R Appell, Nauman Chaudary, Sugeet K Jagpal, Raksha Jain, Adaobi Kanu, Bradley S Quon, John M Reynolds, Charlotte C Teneback, Quynh-Anh Mai, Veronika Shabanova, Paul E Turner, Jonathan L Koff.

Bacteriophage (phage) therapy, which uses lytic viruses as antimicrobials, is a potential strategy to address the antimicrobial resistance crisis. Cystic fibrosis, a disease complicated by recurrent Pseudomonas aeruginosa pulmonary infections, is an example of the clinical impact of antimicrobial resistance. Here, using a personalized phage therapy strategy that selects phages for a predicted evolutionary trade-off, nine adults with cystic fibrosis (eight women and one man) of median age 32 (range 22-46) years were treated with phages on a compassionate basis because their clinical course was complicated by multidrug-resistant or pan-drug-resistant Pseudomonas that was refractory to prior courses of standard antibiotics. The individuals received a nebulized cocktail or single-phage therapy without adverse events. Five to 18 days after phage therapy, sputum Pseudomonas decreased by a median of 104 CFU ml-1, or a mean difference of 102 CFU ml-1 (P = 0.006, two-way analysis of variance with Dunnett's multiple-comparisons test), without altering sputum microbiome, and an analysis of sputum Pseudomonas showed evidence of trade-offs that decreased antibiotic resistance or bacterial virulence. In addition, an improvement of 6% (median) and 8% (mean) predicted FEV1 was observed 21-35 days after phage therapy (P = 0.004, Wilcoxon signed-rank t-test), which may reflect the combined effects of decreased bacterial sputum density and phage-driven trade-offs. These results show that a personalized, nebulized phage therapy trade-off strategy may affect clinical and microbiologic endpoints, which must be evaluated in larger clinical trials.

DOI: https://doi.org/10.1038/s41591-025-03678-8
Sci Rep. 2025 Apr 29. 15(1): 14958

Inflammation, toxicity, and apoptosis reducing potential of bacteriophage Ariobarzanes on intestinal cells infected with Salmonella Typhimurium.

Mina Rahiminejad, Maryam Montaseri, Mohammad Hashem Yousefi, Saeed Nazifi, Jeroen Wagemans, Saeid Hosseinzadeh.

  The emergence of antimicrobial-resistant bacteria has urged researchers to find alternatives or adjunct therapies, such as bacteriophages or phages. This study aimed to investigate the capabilities of Salmonella Typhimurium-specific phage Ariobarzanes in reducing cytotoxicity, invasion, and induction of necrosis and apoptosis caused by Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) ATCC 14,028 infection in the human small intestinal cell line Caco-2. For this purpose, cytotoxicity tests were performed, and the production of inflammatory cytokines interleukin-8 (IL-8) and tumor necrosis factor -alpha (TNF-α) was investigated in phage-treated versus non-treated samples (for 6-hour or 16-hour). The results indicate the success of Ariobarzanes in reducing cytotoxicity in a dose dependently, completely inhibiting Salmonella spp. invasion of Caco-2 cells, reducing Salmonella-induced apoptosis, and necrosis, and also reducing the production and secretion of cytokines IL-8, and TNF-α compared to the bacterial control treatment. Therefore, Ariobarzanes can be introduced as a potential candidate for controlling S. Typhimurium in the agriculture, food, and/or pharmaceutical industries.

Keywords:   Salmonella Typhimurium; Ariobarzanes; Bacteriophage; Cytotoxicity; Inflammatory mediators; Intestinal cells

DOI:  https://doi.org/10.1038/s41598-025-99116-3
Cell Host Microbe. 2025 Apr 21. pii: S1931-3128(25)00135-0. [Epub ahead of print]

A bacteriophage-conditional mouse model reveals the impact of phages within a conventionally colonized gut microbiota.

Hollyn C Franklin, Rita Makhlouf, Anh D Ha, Rogerio A Bataglioli, Zachary R Baker, Sydney A Murphy, Hannah Jirsa, Joshua Heuler, Teresa Southard, Frank O Aylward, Bryan B Hsu.

  The significance of bacteriophages in the gut microbiota remains poorly understood due, in part, to an absence of an animal model that allows for comparative study of conditions with or without phages while retaining the microbial diversity attained by conventional colonization. We describe a mouse model that uses a broadly available chemical compound, acriflavine, to preferentially deplete virulent phages from the gut without significantly impacting gut bacteria. We then show that gut phage density can be reconstituted by oral gavage. Using this bacteriophage-conditional (BaCon) mouse model, we reveal that while phages have comparatively minimal impact during equilibrium conditions, they increase the potency of ampicillin against commensal gut bacteria. Collectively, our work presents an animal model that can be leveraged to conditionally study the role of phages in complex, physiologically relevant systems and further identifies virulent gut phages as potential sources of bacterial variability during major perturbations.

Keywords:  acridine; gut microbiome; lytic phage; mouse model

DOI:  https://doi.org/10.1016/j.chom.2025.04.002
Virology. 2025 Apr 24. pii: S0042-6822(25)00158-8. [Epub ahead of print]608 110545

Identification of a broad-spectrum lytic Bordetella phage and assessments of its potential for combating Bordetella infections.

Xi Huang, Yanyan Hou, Mengfei Zhao, Jian Chen, Zhanwei Zhu, Hanyuan Liu, Minghao Wang, Lin Hua, Huanchun Chen, Bin Wu, Zhong Peng.

  Bordetella bronchiseptica (Bb) is a zoonotic respiratory pathogen that frequently causes infections in farming and companion animals, posing threats to agricultural economics and public health. However, Bb strains are intrinsically resistant to several antibiotics commonly used to treat respiratory infections. Phage therapy has been recognized as a promising strategy to combat bacterial infections. In this study, a novel Bordetella phage, designated PY223, was isolated using Bb strains as indicators. Genome network analysis with different phages showed PY223 was related to 15 viral clusters but was not included in any of these clusters. PY223 did not carry any known genes involved in lysogeny and/or horizontal gene transfer. Host range analysis showed that PY223 exhibited the capacity to lyse 70 Bb strains isolated from pigs and/or cats. Measurement of the one-step growth curve showed that PY223 had an incubation period of 10 min and a rapid growth period of 80 min. The burst size was estimated to be approximately 109 PFU/cell. In addition, PY223 displayed the capacity to inhibit the growth of Bb for up to 17 h. PY223 was stable under environmental temperatures ranging from 4 °C to 60 °C and/or pH values between 5.0 and 9.0. It remained stable even when exposed to UV light for 30 min. Notably, PY223 effectively eliminated Bb biofilms, inhibited the growth of prophage-harboring Bb strains, and cleared Bb from the environment. In vivo testing in mouse models highlighted its excellent potential for treating respiratory Bordetella infections.

Keywords:  Antibacterial activity; Biofilms; Bordetella bronchiseptica; Lytic phage; Mouse models

DOI:  https://doi.org/10.1016/j.virol.2025.110545
Microbiol Resour Announc. 2025 Apr 29. e0027525

Genome sequences of two phages active against cystic fibrosis isolates of Pseudomonas aeruginosa.

Tracey L Peters, Yunxiu He, Amanda M Ward, Nino Mzhavia, Damon W Ellison, Mikeljon P Nikolich, Andrey A Filippov.

  We describe the genomes of two Pseudomonas aeruginosa phages of the genus Bruynoghevirus, WRAIR_EPa83 and WRAIR_EPa87. They consist of 45,622 and 45,077 bp, with 52.52% and 52.11% guanine-cytosine content, contain 81 and 80 coding sequences, two and three tRNA genes, and direct terminal repeats of 183 and 184 bp, respectively.

Keywords:  Bruynoghevirus; Pseudomonas aeruginosa; bacteriophage therapy; clinical trial; cystic fibrosis; drug resistance; lytic phages; phage EPa83 and EPa87 genomes; promising therapeutics

DOI:  https://doi.org/10.1128/mra.00275-25
Curr Opin Gastroenterol. 2025 Apr 28.

Gut-directed therapeutics in inflammatory bowel disease.

Christina Kratschmer, David T Curiel, Matthew A Ciorba.

   PURPOSE OF REVIEW: Tissue-directed therapies (TDTs) provide potential advantages, including improved tolerance, safety, and efficacy. This review provides a conceptual framework for understanding intestinal TDT and summarizes the current landscape of TDT in inflammatory bowel disease (IBD).
RECENT FINDINGS: Vedolizumab, a mAb targeting the gut homing α4β7 integrin, served as revolutionary proof-of-principle for the power of advanced TDT in IBD. The development of other monoclonal antibodies targeting cell adhesion molecules followed including abrilumab (α4β7), etrolizumab (β7), and ontamalimab (MAdCAM-1). MORF-057, an oral small molecule inhibitor of α4β7, is now in development for ulcerative colitis. Efforts have also been made toward gut specific JAK inhibitors. Microbiome-based therapies, including engineered probiotics, bacteriophages, and postbiotics, are gaining interest. There are also a number of innovative drug delivery methods, including engineered yeast, hydrogels, and nanoparticles, and viral-based gene therapy.
SUMMARY: Gut-targeted therapies range from novel variations on traditional drugs (i.e., mAbs and small molecules) to microbiome-based therapeutics and engineered delivery systems. They can be used alone or in combination with currently available therapies. Future directions should focus on the development of tried-and-true modalities (mAbs, small molecules) as well as the microbiome and more innovative delivery systems.

Keywords:  Crohn's disease; biologic; microbiome; small molecule; ulcerative colitis

DOI:  https://doi.org/10.1097/MOG.0000000000001099
Front Immunol. 2025 ;16 1545308

Sequestering survival: sponge-like proteins in phage evasion of bacterial immune defenses.

Lan Wang, Ruoqi Zheng, Leiliang Zhang.

  By executing abortive infection, bacterial immune defense systems recognize phage components and initiate the production of various second messengers that target specific downstream effectors responsible for nucleic acid degradation, membrane destruction, or metabolite depletion. Notably, the sponge-like proteins encoded by phages, such as Tad1, Tad2, and Acb2, can inhibit abortive infection by sequestering, rather than degrading, these bacterial second messengers. This interference disrupts the activation of the effectors involved in the immune response. Most significantly, sponge-like proteins can simultaneously encapsulate diverse signals, effectively preventing the cell suicide mechanisms triggered by different bacterial immune systems, such as the cyclic nucleotide-based antiphage signaling system (CBASS) and Thoeris. The discovery of these sponge-like proteins reveals a remarkable strategy for suppressing innate immunity, ensuring viral replication and propagation. This greatly enhances our understanding of the ongoing arms race between hosts and viruses.

Keywords:  CBASS; Thoeris; cyclic oligonucleotides; phage; sponge-like proteins

DOI:  https://doi.org/10.3389/fimmu.2025.1545308
J Glob Antimicrob Resist. 2025 Apr 26. pii: S2213-7165(25)00088-8. [Epub ahead of print]

Exogenous hydrogen sulfide sensitizes carbapenemase-producing Acinetobacter baumannii to gentamicin.

Nicolas Helsens, Jacqueline Findlay, Maxime Bouvier, Patrice Nordmann.

   OBJECTIVES: Carbapenem-resistant Acinetobacter baumannii pose a major public health threat. These bacteria often display broad-spectrum antibiotic resistance, rendering them resistant to nearly all classes of antibiotics. Hydrogen sulfide (H2S), a compound naturally produced by many bacterial species, has been proposed to exert a protective effect against certain antibiotics. However, A. baumannii does not produced H2S.
METHODS: To investigate the effect of exogenous H2S on antibiotic resistance, several clinical isolates of carbapenemase-producing A. baumannii were cultured under various conditions, including the presence or absence of H2S and/or sub-inhibitory concentrations of gentamicin, azithromycin, ciprofloxacin, tetracycline, and meropenem. Bacterial growth was assessed at multiple time points to evaluate growth dynamics.
RESULTS: Exogenous H2S alone had a limited impact on bacterial growth. However, its addition reduced the minimum inhibitory concentration (MIC) of gentamicin and sensitized the bacteria to sub-inhibitory concentrations of this antibiotic.
CONCLUSION: This study highlights the potential of H2S as an antibiotic potentiator, suggesting that the use of this combination may be a promising strategy for treating pulmonary infections caused by A. baumannii or for preventing colonization on medical devices such as catheters.

Keywords:  A. baumannii; antibiotic resistance; gentamicin; hydrogen sulfide

DOI:  https://doi.org/10.1016/j.jgar.2025.04.018
Nature. 2025 Apr 23.

How to fix a gut microbiome ravaged by antibiotics.

Heidi Ledford.



Keywords:  Antibiotics; Microbiology; Microbiome

DOI:  https://doi.org/10.1038/d41586-025-01313-7
J Clin Med. 2025 Apr 14. pii: 2678. [Epub ahead of print]14(8):

Key Insights into Gut Alterations in Metabolic Syndrome.

Adrian Boicean, Cristian Ichim, Sabina-Maria Sasu, Samuel Bogdan Todor.

  Over time, extensive research has underscored the pivotal role of gut microbiota in the onset and progression of various diseases, with a particular focus on fecal microbiota transplantation (FMT) as a potential therapeutic approach. The practice of transferring fecal matter from a healthy donor to a patient provides valuable insights into how alterations in gut microbiota can impact disease development and how rectifying dysbiosis may offer therapeutic benefits. Re-establishing a balanced symbiotic relationship in the gastrointestinal tract has shown positive results in managing both intestinal and systemic conditions. Currently, one of the most pressing global health issues is metabolic syndrome-a cluster of conditions that includes insulin resistance, lipid imbalances, central obesity and hypertension. In this context, FMT has emerged as a promising strategy for addressing key components of metabolic syndrome, such as improving insulin sensitivity, body weight and lipid profiles. However, further well-structured studies are needed to refine treatment protocols and establish the long-term safety and efficacy of this intervention.

Keywords:  FMT; dyslipidemia; gut; hypertension; obesity

DOI:  https://doi.org/10.3390/jcm14082678
Microorganisms. 2025 Apr 09. pii: 852. [Epub ahead of print]13(4):

Staphylococcus aureus Biofilm-Associated Infections: Have We Found a Clinically Relevant Target?

Karen E Beenken, Mark S Smeltzer.

  Staphylococcus aureus is one of the most diverse bacterial pathogens. This is reflected in its ability to cause a wide array of infections and in genotypic and phenotypic differences between clinical isolates that extend beyond their antibiotic resistance status. Many S. aureus infections, including those involving indwelling medical devices, are therapeutically defined by the formation of a biofilm. This is reflected in the number of reports focusing on S. aureus biofilm formation and biofilm-associated infections. These infections are characterized by a level of intrinsic resistance that compromises conventional antibiotic therapy irrespective of acquired resistance, suggesting that an inhibitor of biofilm formation would have tremendous clinical value. Many reports have described large-scale screens aimed at identifying compounds that limit S. aureus biofilm formation, but relatively few examined whether the limitation was sufficient to overcome this intrinsic resistance. Similarly, while many of these reports examined the impact of putative inhibitors on S. aureus phenotypes, very few took a focused approach to identify and optimize an effective inhibitor of specific biofilm-associated targets. Such approaches are dependent on validating a target, hopefully one that is not restricted by the diversity of S. aureus as a bacterial pathogen. Rigorous biological validation of such a target would allow investigators to virtually screen vast chemical libraries to identify potential inhibitors that warrant further investigation based on their predicted function. Here, we summarize reports describing S. aureus regulatory loci implicated in biofilm formation to assess whether they are viable targets for the development of an anti-biofilm therapeutic strategy with an emphasis on whether sarA has been sufficiently validated to warrant consideration in this important clinical context.

Keywords:  Staphylococcus aureus; agr; biofilm; osteomyelitis; protease; regulation; sarA; sigB; xerC

DOI:  https://doi.org/10.3390/microorganisms13040852
Research (Wash D C). 2025 ;8 0657

The Discovery of Phages in the Substantia Nigra and Its Implication for Parkinson's Disease.

Yun Zhao, Changxian Xiong, Bingwei Wang, Daotong Li, Jiarui Liu, Shizhang Wei, Yujia Hou, Yuan Zhou, Ruimao Zheng.

Background: A century ago, a mystery between a virus and Parkinson's disease (PD) was described. Owing to the limitation of human brain biopsy and the challenge of electron microscopy in observing virions in human brain tissue, it has been difficult to study the viral etiology of PD. Recent discovery of virobiota reveals that viruses coexist with humans as symbionts. Newly developed transcriptomic sequencing and novel bioinformatic approaches for mining the encrypted virome in human transcriptome make it possible to study the relationship between symbiotic viruses and PD. Nevertheless, whether viruses exist in the human substantia nigra (SN) and whether symbiotic viruses underlie PD pathogenesis remain unknown. Methods: We collected current worldwide human SN transcriptomic datasets from the United States, the United Kingdom, the Netherlands, and Switzerland. We used bioinformatic approaches including viruSITE and the Viral-Track to identify the existence of viruses in the SN of patients. The comprehensive RNA sequencing-based virome analysis pipeline was used to characterize the virobiota in the SN. The Pearson's correlation analysis was used to examine the association between the viral RNA fragment counts (VRFCs) and PD-related human gene sequencing reads in the SN. The differentially expressed genes (DEGs) in the SN between PD patients and non-PD individuals were used to examine the molecular signatures of PD and also evaluate the impact of symbiotic viruses on the SN. Findings: We observed the existence of viruses in the human SN. A dysbiosis of virobiota was found in the SN of PD patients. A marked correlation between VRFC and PD-related human gene expression was detected in the SN of PD patients. These PD-related human genes correlated to VRFC were named as the virus-correlated PD-related genes (VPGs). We identified 3 bacteriophages (phages), including the Proteus phage VB_PmiS-Isfahan, the Escherichia phage phiX174, and the Lactobacillus phage Sha1, that might impair the gene expression of neural cells in the SN of PD patients. The Proteus phage VB_PmiS-Isfahan was a common virus in the SN of patients from the United Kingdom, the Netherlands, and Switzerland. VPGs and DEGs together highlighted that the phages might dampen dopamine biosynthesis and weaken the cGAS-STING function. Interpretation: This is the first study to discover the involvement of phages in PD pathogenesis. A lifelong low symbiotic viral load in the SN may be a contributor to PD pathogenesis. Our findings unlocked the black box between brain virobiota and PD, providing a novel insight into PD etiology from the perspective of phage-human symbiosis.

DOI: https://doi.org/10.34133/research.0657
Curr Urol. 2025 Mar;19(2): 125-132

Bacteriophage therapy in women with chronic recurrent cystitis caused by multidrug-resistant bacteria: A prospective, observational, comparative study.

Denis Krakhotkin, Nikolai Iglovikov, Gideon Blecher, Vladimir Chernylovskyi, Francesco Greco, Svetlana A Gayvoronskaya, Amr El Meliegy.

   Objectives: The aim of this study was to evaluate the effects of the combination of bacteriophage therapy with antibiotics and bacteriophage treatment alone on relieving clinical symptoms of chronic recurrent cystitis caused by multidrug-resistant bacteria.
Materials and methods: This clinical trial compared the treatment methods of 217 female patients with chronic recurrent cystitis caused by multidrug-resistant bacteria, who were investigated from June 2020 to May 2023. Patients were allocated into 4 groups: group I: received bacteriophage (Sextaphage) therapy alone; group II: received a combination of bacteriophages (Sextaphage) and furazidin; group III: received a combination of bacteriophage (Sextaphage) and furazidin with cefixime; and group IV: received furazidin and cefixime (without bacteriophage). The primary outcome included changes in the acute cystitis symptom scale and the pain visual analog scale, which were completed on days 7 and 14 following treatment. Secondary outcome measures included bladder diary records of urinary symptoms, median voided volumes, level of bacteriuria, and degree of leukocyturia.
Results: Initially, 217 female patients were presented during baseline visits. Those who did not meet the criteria inclusions were excluded, and 178 female patients were included in the final analysis. Statistically significant improvements from baseline in acute cystitis symptom scale scores for differential, typical symptoms, and quality of life domains were observed after 14 days of treatment in groups II, III, and IV. The pain level measured on the 14th day with the visual analog scale significantly decreased in groups II, III, and IV compared with group I. The patients of group I had a reduction of mean level bacteriuria of Escherichia coli from 106 to 102 CFU/mL at 14 days of therapy. Significant improvement of voided volume from baseline was observed in groups II, III, and IV. Episodes of urinary frequency, both daytime and night-time, reduced significantly from baseline in all 4 groups only at 14 days of treatment.
Conclusions: Bacteriophage cocktail alone or with antibiotics may improve clinical symptoms in women with chronic recurrent cystitis caused by multidrug-resistant bacterial pathogens. In addition to improving clinical symptoms, the therapy with a phage cocktail may restore antibiotic sensitivity and increase the efficacy of antimicrobial agents.

Keywords:  Antibiotic resistance; Bacteriophages; Chronic recurrent cystitis; Urinary tract infection

DOI:  https://doi.org/10.1097/CU9.0000000000000268
Healthcare (Basel). 2025 Apr 17. pii: 923. [Epub ahead of print]13(8):

New Therapeutic Challenges in Pediatric Gastroenterology: A Narrative Review.

Valeria Dipasquale, Claudio Romano.

  Pediatric gastroenterology is entering a pivotal phase marked by significant challenges and emerging opportunities in treating conditions like celiac disease (CeD), eosinophilic esophagitis (EoE), inflammatory bowel disease (IBD), and autoimmune hepatitis (AIH) pose significant clinical hurdles, but new therapeutic avenues are emerging. Advances in precision medicine, particularly proteomics, are reshaping care by tailoring treatments to individual patient characteristics. For CeD, therapies like gluten-degrading enzymes (latiglutenase, Kuma030) and zonulin inhibitors (larazotide acetate) show promise, though clinical outcomes are inconsistent. Immunotherapy and microbiota modulation, including probiotics and fecal microbiota transplantation (FMT), are also under exploration, with potential benefits in symptom management. Transglutaminase 2 inhibitors like ZED-1227 could help prevent gluten-induced damage. Monoclonal antibodies targeting immune pathways, such as AMG 714 and larazotide acetate, require further validation in pediatric populations. In EoE, biologics like dupilumab, cendakimab, dectrekumab (IL-13 inhibitors), and mepolizumab, reslizumab, and benralizumab (IL-5/IL-5R inhibitors) show varying efficacy, while thymic stromal lymphopoietin (TSLP) inhibitors like tezepelumab are also being investigated. These therapies require more pediatric-specific research to optimize their use. For IBD, biologics like vedolizumab, ustekinumab, and risankizumab, as well as small molecules like tofacitinib, etrasimod, and upadacitinib, are emerging treatments. New medications for individuals with refractory or steroid-dependent AIH have been explored. Personalized therapy, integrating precision medicine, therapeutic drug monitoring, and lifestyle changes, is increasingly guiding pediatric IBD management. This narrative review explores recent breakthroughs in treating CeD, EoE, IBD, and AIH, with a focus on pediatric studies when available, and discusses the growing role of proteomics in advancing personalized gastroenterological care.

Keywords:  autoimmune hepatitis; biologics; celiac disease; enzyme therapy; eosinophilic esophagitis; immunotherapy; inflammatory bowel disease; microbiome; personalized medicine; proteomics; small molecules

DOI:  https://doi.org/10.3390/healthcare13080923
Talanta. 2025 Apr 22. pii: S0039-9140(25)00699-X. [Epub ahead of print]294 128209

Phage/aptamer dual-encoded hydrogel arrays integrated with microfluidic platforms for simultaneous detection of multiple food pathogens.

Jie Xu, Siwei Zhou, Yuqi Zhang, Huihui Wu, Tianhua Li, Lei Tan, Ning Gan, Jincan He.

  Food pathogens pose significant threats to public health. This study presents a universal, sensitive and time-efficient microfluidic chip electrophoresis (MCE) platform for simultaneously detecting multiple food pathogens based on phage/aptamer dual-encoded hydrogel arrays. The arrays are comprised of "all-in-one" hydrogel slices embedded with the capturing probe of specific phages and sensing probe of ATP aptamer/complementary chain (A-Apt/cDNA) hybrid structures. The live bacteria are specifically captured and lysed by the corresponding phages to generate copious amounts of ATP. The ATP further combines with the A-Apt/cDNA hybrids to release the cDNA strands with various lengths from the hydrogel pores into the supernatant. Therefore, cDNA strands whose lengths are specific for each bacteria function as markers for ATP, the level of which represents the number of living bacteria. The qualitation and quantification of multiple bacteria is realized by isolating and analyzing various cDNA using MCE. Taking three food pathogens (i.e., E. coli, Salmonella typhimurium, Staphylococcus aureus) as target models, the platform were performed within 60 min, with detection limits of 20 CFU/mL, 30 CFU/mL and 15 CFU/mL, respectively. This study offers a universal and rapid strategy for multiple food pathogens analysis.

Keywords:  Aptamer; Foodborne pathogens; Hydrogel; Microfluidic chip; Phage; Simultaneous detection

DOI:  https://doi.org/10.1016/j.talanta.2025.128209
FEMS Microbiol Ecol. 2025 Apr 29. pii: fiaf046. [Epub ahead of print]

Exploring and Evaluating Microbiome Resilience in the Gut.

Huimin Zhou, Li Tang, Kristin A Fenton, Xiaobo Song.

  The gut ecosystem is closely related to human gastrointestinal health and overall wellness. Microbiome resilience refers to the capability of a microbial community to resist or recover from perturbations to its original state of balance. So far, there is no consensus on the criteria for assessing microbiome resilience. This article provides new insights into the metrics and techniques for resilience assessment. We discussed several potential parameters, such as microbiome structure, keystone species, biomarkers, persistence degree, recovery rate, and various research techniques in microbiology, metagenomics, biochemistry and dynamic modeling. The article further explores the factors that influence the gut microbiome resilience. The microbiome structure (i.e. abundance and diversity), keystone species and microbe-microbe interplays determine microbiome resilience. Microorganisms employ a variety of mechanisms to achieve the microbiome resilience, including flexible metabolism, quorum sensing, functional redundancy, microbial cooperation and competition. Host-microbe interactions play a crucial role in maintaining microbiome stability and functionality. Unlike other articles, we focus on the regulation of host immune system on microbiome resilience. The immune system facilitates bacterial preservation and colonization, community construction, probiotic protection and pathogen elimination through the mechanisms of immunological tolerance, immune-driven microbial compartmentalization and immune inclusion and exclusion. Microbial immunomodulation indirectly modulates microbiome resilience.

Keywords:  host-microbe interactions; microbe-microbe interplays; microbiome resilience; microbiome structure and keystone species

DOI:  https://doi.org/10.1093/femsec/fiaf046