An enterococcal phage protein inhibits type IV restriction enzymes involved in antiphage defense DOI Creative Commons
Nathan P. Bullen, Cydney N. Johnson, Shelby E. Andersen

et al.

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

Gamma-Mobile-Trio systems are mobile elements rich in bacterial defensive and offensive tools DOI
Tridib Mahata,

Katarzyna Kanarek,

Moran G. Goren

et al.

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

Published: Oct. 23, 2024

Language: Английский

Citations

5
Phage-Defense Systems Are Unlikely to Cause Cell Suicide DOI Creative Commons
Laura Fernández-García, Thomas K. Wood

Viruses, Journal Year: 2023, Volume and Issue: 15(9), P. 1795 - 1795

Published: Aug. 24, 2023

As new phage-defense systems (PDs) are discovered, the overlap between their mechanisms and those of toxin/antitoxin (TAs) is becoming clear in that both use similar means to reduce cellular metabolism; for example, have members deplete energetic compounds (e.g., NAD+, ATP) nucleic acids, inflict membrane damage. Moreover, TAs PDs rather than altruistically killing host limit phage propagation (commonly known as abortive infection), metabolism since phages propagate less slow-growing cells, slow growth facilitates interaction multiple systems.

Language: Английский

Citations

11
Discovery of antiphage systems in the lactococcal plasmidome DOI Creative Commons
Andriana Grafakou, Cas Mosterd, Matthias H. Beck

et al.

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 52(16), P. 9760 - 9776

Published: Aug. 9, 2024

Abstract Until the late 2000s, lactococci substantially contributed to discovery of various plasmid-borne phage defence systems, rendering these bacteria an excellent antiphage resource. Recently, there has been a resurgence interest in identifying novel systems lactic acid owing recent reports so-called ‘defence islands’ diverse bacterial genera. Here, 321 plasmid sequences from 53 lactococcal strains were scrutinized for presence systems. Systematic evaluation 198 candidates facilitated seven not previously described as well five which homologues had other bacteria. All confer resistance against most prevalent phages, and act post DNA injection, while all except one behave like abortive infection Structure domain predictions provided insights into their mechanism action allow grouping several genetically distinct Although rare within our collection, appear be widespread among This study highlights plasmids rich repository yet undiscovered

Language: Английский

Citations

4
Principles of bacterial innate immunity against viruses DOI Creative Commons
Michael T. Laub, Athanasios Typas

Current Opinion in Immunology, Journal Year: 2024, Volume and Issue: 89, P. 102445 - 102445

Published: Aug. 1, 2024

All organisms must defend themselves against viral predators. This includes bacteria, which harbor immunity factors such as restriction-modification systems and CRISPR-Cas systems. More recently, a plethora of additional defense have been identified, revealing richer, more sophisticated immune system than previously appreciated. Some these newly identified distant homologs in mammals, suggesting an ancient evolutionary origin some facets mammalian immunity. An even broader conservation exists at the level how operate. Here, we focus this level, reviewing key principles high-level attributes innate bacteria that are shared with immunity, while also noting differences, particular emphasis on cells sense infection.

Language: Английский

Citations

4
Functional characterization of Mrr-family nuclease SLL1429 involved in MMC and phage resistance DOI

Yanchao Gu,

Jingling Xu,

Yufei Zhao

et al.

Microbiological Research, Journal Year: 2025, Volume and Issue: 296, P. 128123 - 128123

Published: Feb. 27, 2025

Language: Английский

Citations

0
Filamentation activates bacterial Avs5 antiviral protein DOI Creative Commons
Yiqun Wang, Yuqing Tian, Xu Yang

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 11, 2025

Bacterial antiviral STANDs (Avs) are evolutionarily related to the nucleotide-binding oligomerization domain (NOD)-like receptors widely distributed in immune systems across animals and plants. EfAvs5, a type 5 Avs from Escherichia fergusonii, contains an N-terminal SIR2 effector domain, NOD, C-terminal sensor conferring protection against diverse phage invasions. Despite established roles of STAND prokaryotic eukaryotic immunity, mechanism underlying their collaboration remains unclear. Here we present cryo-EM structures EfAvs5 filaments, elucidating mechanisms dimerization, filamentation, filament bundling, ATP binding, NAD+ hydrolysis, all which crucial for anti-phage defense. The NOD domains engage intra- inter-dimer interaction form individual filament, while outward contribute bundle formation. Filamentation potentially stabilizes dimeric configuration, thereby activating NADase activity EfAvs5. Furthermore, identify nucleotide kinase gp1.7 T7 as activator demonstrating its ability induce filamentation activity. Together, uncover assembly Avs5 unique switch enzyme activities perform defenses. protect Here, authors reveal that forms clustered filaments hydrolysis can be activated by protein, mechanism.

Language: Английский

Citations

0
Invasive bacteriophages between a bell and a hammer: a comprehensive review of pharmacokinetics and bacterial defense systems DOI Creative Commons

Mohammed F Hamdi,

Alyaa Abdulhussein Alsaedi,

Alaa Qasim Hayder

et al.

Discover Life, Journal Year: 2025, Volume and Issue: 55(1)

Published: April 3, 2025

Language: Английский

Citations

0
Bacteria conjugate ubiquitin-like proteins to interfere with phage assembly DOI Creative Commons
Jens Hör, Sharon G. Wolf, Rotem Sorek

et al.

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

Published: Sept. 4, 2023

Abstract Multiple immune pathways in humans conjugate ubiquitin-like proteins to virus and host molecules as a means of antiviral defense. Here we studied an anti-phage defense system bacteria, comprising protein, ubiquitin-conjugating enzymes E1 E2, deubiquitinase. We show that during phage infection, this specifically conjugates the protein central tail fiber, at tip is essential for assembly well recognition target receptor. Following cells encoding release mixture partially assembled, tailless particles, fully assembled phages which fiber obstructed by covalently attached protein. These exhibit severely impaired infectivity, explaining how protects bacterial population from spread infection. Our findings demonstrate conjugation strategy conserved across tree life.

Language: Английский

Citations

9
Anti-viral defence by an mRNA ADP-ribosyltransferase that blocks translation DOI Creative Commons
Christopher N. Vassallo, Christopher R. Doering, Michael T. Laub

et al.

Nature, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 23, 2024

Abstract Host–pathogen conflicts are crucibles of molecular innovation 1,2 . Selection for immunity to pathogens has driven the evolution sophisticated mechanisms throughout biology, including in bacterial defence against bacteriophages 3 Here we characterize widely distributed anti-phage system CmdTAC, which provides robust infection by T-even family phages 4 Our results support a model CmdC detects sensing viral capsid proteins, ultimately leading activation toxic ADP-ribosyltransferase effector protein, CmdT. We show that newly synthesized protein triggers dissociation chaperone from CmdTAC complex, destabilization and degradation antitoxin CmdA, with consequent liberation CmdT ADP-ribosyltransferase. Notably, does not target DNA or structured RNA, known targets other ADP-ribosyltransferases. Instead, modifies N6 position adenine GA dinucleotides within single-stranded RNAs, arrest mRNA translation inhibition replication. work reveals novel mechanism anti-viral previously unknown but broadly class ADP-ribosyltransferases mRNA.

Language: Английский

Citations

2
GMT systems define a new class of mobile elements rich in bacterial defensive and offensive tools DOI Creative Commons
Tridib Mahata,

Katarzyna Kanarek,

Moran G. Goren

et al.

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

Citations

6