Diverse Antiphage Defenses Are Widespread Among Prophages and Mobile Genetic Elements

Annual Review of Virology, Journal Year: 2024, Volume and Issue: 11(1), P. 343 - 362

Published: July 1, 2024

Bacterial viruses known as phages rely on their hosts for replication and thus have developed an intimate partnership over evolutionary time. The survival of temperate phages, which can establish a chronic infection in genomes are maintained quiescent state prophage, is tightly coupled with the bacterial hosts. As result, prophages encode diverse antiphage defense arsenal to protect themselves host they reside from further phage infection. Similarly, success prophage-related elements such phage-inducible chromosomal islands directly tied host, also been shown numerous defenses. Here, we describe current knowledge defenses encoded by mobile genetic elements.

Language: Английский

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Gamma-Mobile-Trio systems are mobile elements rich in bacterial defensive and offensive tools

Nature Microbiology, Journal Year: 2024, Volume and Issue: 9(12), P. 3268 - 3283

Published: Oct. 23, 2024

Language: Английский

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Globally occurring pelagiphage infections create ribosome-deprived cells

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 2, 2024

Phages play an essential role in controlling bacterial populations. Those infecting Pelagibacterales (SAR11), the dominant bacteria surface oceans, have been studied silico and by cultivation attempts. However, little is known about quantity of phage-infected cells environment. Using fluorescence situ hybridization techniques, we here show pelagiphage-infected SAR11 across multiple global ecosystems present evidence for tight community control pelagiphages on hosts a case study. Up to 19% were during phytoplankton bloom, coinciding with ~90% reduction cell abundance within 5 days. Frequently, fraction infected devoid detectable ribosomes, which appear be yet undescribed possible stage pelagiphage infection. We dubbed such zombies propose, among other explanations, mechanism ribosomal RNA used as resource synthesis new phage genomes. On scale, detected zombie Atlantic, Pacific, Southern Oceans. Our findings illuminate important impact populations unveil presence ribosome-deprived part infection cycle.

Language: Английский

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Implications of lytic phage infections inducing persistence

Current Opinion in Microbiology, Journal Year: 2024, Volume and Issue: 79, P. 102482 - 102482

Published: May 6, 2024

Language: Английский

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GMT systems define a new class of mobile elements rich in bacterial defensive and offensive tools

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: March 28, 2023

Abstract Conflicts between bacteria and their rivals led to an evolutionary arms race the development of bacterial immune systems. Although diverse immunity mechanisms were recently identified, many remain unknown, dissemination within is poorly understood. Here, we describe a widespread genetic element, defined by presence Gamma-Mobile-Trio (GMT) proteins, that serves as survival kit. We show GMT-containing genomic islands are active mobile elements with cargo comprising various anti-phage defense systems, in addition antibacterial type VI secretion system (T6SS) effectors antibiotic resistance genes. identify four new systems encoded GMT islands. A thorough investigation one reveals it triggered phage capsid protein induce cell dormancy. Our findings underscore need broaden concept ‘defense islands’ include also offensive tools, such T6SS effectors, they share same defensive tools for dissemination.

Language: Английский

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Phages Produce Persisters

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 17, 2023

SUMMARY Bacteria primarily encounter stress, and, arguably, their greatest threats are phages. It is often assumed that those bacteria escape phage attack have mutated; however, another possibility a subpopulation forms the dormant persister state, in manner similar to demonstrated for bacterial cells undergoing nutritive, oxidative, and antibiotic stress. Persister do not undergo mutation survive lethal conditions by ceasing growth transiently. Slower dormancy play key physiological role as they allow host defense systems more time clear infection. Here we investigated how lytic infection isolating surviving from plaques of T2, T4, lambda (cI mutant) virulent We found can both (i.e., become resistant) without persistent). Specifically, whereas T4-resistant lambda-resistant with over 100,000-fold less sensitivity were isolated obvious genetic mutations (e.g., causing mucoidy), also after T2 no significant mutation, retain wild-type sensitivity, doses antibiotics. Corroborating this, adding resulted 137,000-fold survival compared addition exponentially-growing cells. Phage treatments Klebsiella pneumonia Pseudomonas aeruginosa generated Hence, along resistant strains, form during

Language: Английский

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Globally occurring pelagiphage infections create ribosome-deprived cells

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: March 13, 2024

Phages play an essential role in controlling bacterial populations. Those infecting Pelagibacterales (SAR11), the dominant bacteria surface oceans, have been studied in silico and by cultivation attempts. However, little is known about quantity of phage-infected cells environment. Using fluorescence situ hybridization techniques, we here show pelagiphage-infected SAR11 across multiple global ecosystems present evidence for tight community control pelagiphages on hosts a case study. Up to 19% were during phytoplankton bloom, coinciding with ~ 90% reduction cell abundance within five days. Frequently, fraction infected devoid detectable ribosomes, which appear be yet undescribed possible stage pelagiphage infection. We dubbed those ‘zombies’ propose, among other explanations, mechanism ribosomal RNA used as resource synthesis new phage genomes. On scale, detected zombie Atlantic, Pacific, Southern Oceans. Our findings illuminate important impact populations unveil presence ribosome-deprived part infection cycle.

Language: Английский

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An enterococcal phage protein inhibits type IV restriction enzymes involved in antiphage defense

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 13, 2024

The prevalence of multidrug resistant (MDR) bacterial infections continues to rise as the development antibiotics needed combat these remains stagnant. MDR enterococci are a major contributor this crisis. A potential therapeutic approach for combating is bacteriophage (phage) therapy, which uses lytic viruses infect and kill pathogenic bacteria. While phages that lyse some strains have been identified, other display high levels resistance mechanisms underlying poorly defined. Here, we use CRISPR interference (CRISPRi) screen identify genetic locus found on mobilizable plasmid from Enterococcus faecalis involved in phage resistance. This encodes putative serine recombinase followed by Type IV restriction enzyme (TIV-RE) show restricts replication phi47 vancomycin-resistant E. faecalis. We further find evolves overcome acquiring missense mutation TIV-RE inhibitor protein. inhibitor, termed type inhibiting factor (tifA), binds inactivates diverse TIV-REs. Overall, our findings advance understanding defense drug-resistant provide mechanistic insight into how evolve antiphage systems.

Language: Английский

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Conformational change as a mechanism for toxin activation in bacterial toxin-antitoxin systems

Journal of Virology, Journal Year: 2024, Volume and Issue: 98(11)

Published: Oct. 24, 2024

ABSTRACT Toxin/antitoxin (TA) systems are present in nearly every prokaryotic genome and play the important physiological roles of phage inhibition by reducing metabolism (this includes persistence for extreme case complete cessation metabolism), genetic element stabilization, biofilm formation. TA have also been incorporated into other cell systems, such as CRISPR-Cas quorum sensing. For simplest best-studied case, proteinaceous toxins antitoxins (i.e., type II), toxin activity is masked direct binding antitoxin. A long-standing, unresolved question field how activated when bound to at nanomolar affinity. The current paradigm envisions preferential degradation antitoxin a protease, but this highly unlikely that protease cannot discriminate between because both structured. Strikingly, recent results from several studies show one likely mechanism activation conformational changes complex result release or protein trigger, phages, thermally-driven refolding dynamics.

Language: Английский

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Diversity and abundance of ring nucleases in type III CRISPR-Cas loci

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 25, 2024

Summary Most type III CRISPR-Cas systems facilitate immune responses against invading mobile genetic elements such as phages by generating cyclic oligoadenylates (cOAs). Downstream effectors activated cOAs are typically non-specific proteins that induce damage to essential cellular components, thereby preventing phage epidemics. Due these toxic effects, it is crucial the production and concentration of remain under tight regulatory control during infection-free periods or when deactivating response after clearing an infection. Type CRISPR loci often encode enzymes known ring nucleases (RNs) bind degrade specific cOAs, while some auto-deactivating. Despite discovery several classes RNs, a comprehensive bioinformatic analysis in this context lacking. Here, we examined 38,742 prokaryotic genomes provide global overview loci, focussing on predicted RNs. The candidate RNs Csx16 Csx20 confirmed active enzymes, joining Crn1-3. Distributions patterns co-occurrence associated explored, allowing conclusion sizeable majority regulate cOA levels degrading signalling molecules, which has implications for cell fate following viral

Language: Английский

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