Phage therapy

Nature Reviews Methods Primers, Год журнала: 2025, Номер 5(1)

Опубликована: Фев. 13, 2025

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Evolution and ecology of anti-defence systems in phages and plasmids

Current Biology, Год журнала: 2025, Номер 35(1), С. R32 - R44

Опубликована: Янв. 1, 2025

Язык: Английский

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Capturing dynamic phage-pathogen coevolution by clinical surveillance

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 29, 2025

Abstract Bacteria harness diverse defense systems that protect against phage predation 1 , many of which are encoded on horizontally transmitted mobile genetic elements (MGEs) 2 . In turn, phages evolve counter-defenses 3 driving a dynamic arms race remains underexplored in human disease contexts. For the diarrheal pathogen Vibrio cholerae higher burden its lytic phage, ICP1, patient stool correlates with reduced severity 4 However, direct molecular evidence phage-driven selection epidemic V. has not been demonstrated. Here, through clinical surveillance cholera-endemic Bangladesh, we capture acquisition parasitic anti-phage MGE, PLE11, initiated selective sweep coinciding largest cholera outbreak recent records. PLE11 exhibited potent activity co-circulating explaining rapid and dominating emergence. We identify PLE11-encoded Rta as novel responsible provide restricts tail assembly. Using experimental evolution, predict counteradaptations document eventual emergence ICP1 achieves convergent evolutionary outcome. By probing how PLEs hijack structural proteins to drive their horizontal transmission while simultaneously restricting assembly, discover manipulate assembly construct chimeric tails comprised MGE phage-encoded proteins. Collectively, our findings reveal basis natural globally significant virus clinically relevant context.

Язык: Английский

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Phages carry orphan antitoxin-like enzymes to neutralize the DarTG1 toxin-antitoxin defense system

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 13, 2025

The astounding number of anti-phage defenses encoded by bacteria is countered an elaborate set phage counter-defenses, though their evolutionary origins are often unknown. Here, we report the discovery orphan antitoxin counter-defense element in T4-like phages that can overcome bacterial toxin-antitoxin defense system, DarTG1. DarT1 toxin, ADP-ribosyltransferase, modifies DNA to prevent replication while its cognate antitoxin, DarG1, a NADAR superfamily ADP-ribosylglycohydrolase reverses these modifications uninfected bacteria. We show some carry DarG1-like domain protein, which term anti-DarT factor (AdfN), removes ADP-ribose from during infection thereby enabling DarTG1-containing find divergent proteins unrelated likewise exhibit anti-DarTG1 activity, underscoring importance ADP-ribosylation bacterial-phage interactions, and revealing function substantial subset superfamily. Toxin-antitoxin systems make up branch immune system. Johannesman et al demonstrate have co-opted counter ADP-ribosyltransferase

Язык: Английский

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A Class 1 OLD family nuclease encoded by Vibrio cholerae is countered by a vibriophage-encoded direct inhibitor

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 6, 2025

Bacteria are constantly threatened by their viral predators (phages), which has resulted in the development of defense systems for bacterial survival. One family found widely across bacteria OLD (for overcoming lysogeny defect) nucleases. Despite recent discoveries regarding Class 2 and 4 nucleases how phages overcome them, 1 warrant further study as there only been one anti-phage nuclease described to date. Here, we identify Vibrio cholerae- encoded Vc describe its disruption genome replication lytic vibriophage ICP1. Furthermore, examine vitro activity, identifying a DNA nickase. Finally, first direct inhibitor nuclease, ICP1-encoded Oad1. Our research illuminates nucleases' role phage explores dynamic arms race between V. cholerae predatory

Язык: Английский

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Semantics Count in the Description of the Interactions Between Bacteria and Bacteriophage

PHAGE, Год журнала: 2025, Номер unknown

Опубликована: Янв. 28, 2025

Язык: Английский

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Study of the probability of resistance to phage infection in a collection of clinical isolates of P s eudomonas aeruginosa in relation to the presence of Pf phages

Microbiology Spectrum, Год журнала: 2025, Номер unknown

Опубликована: Фев. 5, 2025

ABSTRACT Pseudomonas aeruginosa is a bacterial pathogen that major cause of lung infections in cystic fibrosis (CF) and other patients. Isolates P. from CF patients commonly carry filamentous phages (Pf phages), which constitute family temperate known to be related biofilm production antibiotic sequestration. In this study, we identified 12 new Pf phage genomes collection clinical isolates Study the anti-phage defense systems revealed presence 89 such systems, eight were encoded genomes. Finally, although weak relation between resistance infection number was detected, it observed these phages. IMPORTANCE Bacteria harbor wide range mechanisms avoid hamper application therapy because they can lead rapid acquisition resistance. found genome presents 56% . The high prevalence underlines importance our findings about newly discovered role infections. Thus, knowledge anti-defense system could useful assessing possible treat an infectious disease.

Язык: Английский

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Phage treatment of multidrug-resistant bacterial infections in humans, animals, and plants: The current status and future prospects

Infectious Medicine, Год журнала: 2025, Номер 4(1), С. 100168 - 100168

Опубликована: Фев. 6, 2025

Phages, including the viruses that lyse bacterial pathogens, offer unique therapeutic advantages, their capacity to antibiotic-resistant bacteria and disrupt biofilms without harming host microbiota. The lack of new effective antibiotics growing limitations existing have refocused attention on phage therapy as an option in complex clinical cases such burn wounds, cystic fibrosis, pneumonia. This review describes preclinical studies which has been both human veterinary medicine, agricultural context. In addition, critical challenges, narrow range bacteriophages, possibility resistance, regulatory constraints widespread use therapy, are addressed. Future directions include optimizing through strategies ranging from cocktails broadening genetic modification, using phages vaccines or biocontrol agents. future, if can be efficiently delivered, maintained a stable state, phage-antibiotic synergy achieved, will much needed treatment options. However, successful implementation within current standards practice also require considerable development infrastructure greater public acceptance. closing, this highlights promise backup substitute for antibiotics. It proposes role significant adjunct to, even replacement for, treating multidrug-resistant infections.

Язык: Английский

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Metagenomic selections reveal diverse antiphage defenses in human and environmental microbiomes

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

To prevent phage infection, bacteria have developed an arsenal of antiphage defense systems. Using functional metagenomic selections, we identified new examples these systems from human fecal, oral, and grassland soil microbiomes. Our selections in Escherichia coli revealed over 200 putative defenses 14 diverse bacterial phyla, highlighting the broad phylogenetic interoperability Many were unrecognizable based on sequence or predicted structure, so could only be via assays. In mechanistic studies, show that some encode nucleases degrade covalently modified DNA, but which accommodate chemical modifications. We also identify outer membrane proteins adsorption a set previously unknown with profiles modalities. Most acted against at least two phages, indicating broadly acting are widely distributed among non-model bacteria.

Язык: Английский

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Surface-mediated bacteriophage defense incurs fitness tradeoffs for interbacterial antagonism

The EMBO Journal, Год журнала: 2025, Номер unknown

Опубликована: Март 10, 2025

Язык: Английский

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