The recombination efficiency of the bacterial integron depends on the mechanical stability of the synaptic complex DOI Creative Commons
Ekaterina Vorobevskaia, Céline Loot, Didier Mazel

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(50)

Published: Dec. 13, 2024

Multiple antibiotic resistances are a major global health threat. The predominant tool for adaptation in Gram-negative bacteria is the integron. Under stress, it rearranges gene cassettes to offer an escape using tyrosine recombinase IntI, recognizing folded DNA hairpins, attC sites. Four recombinases and two sites form synaptic complex. Yet, unclear reasons, recombination efficiency varies greatly. Here, we established optical tweezers force spectroscopy assay probe complex stability revealed, seven combinations of sites, significant variability mechanical stability. We found strong correlation between vivo, indicating regulatory mechanism from structure macromolecular Taking into account known forces during metabolism, propose that variation integron vivo mediated by anticipate further processes also affected their corresponding

Language: Английский

Hijackers, hitchhikers, or co-drivers? The mysteries of mobilizable genetic elements DOI Creative Commons
Manuel Ares-Arroyo, Charles Coluzzi, Jorge A. Moura de Sousa

et al.

PLoS Biology, Journal Year: 2024, Volume and Issue: 22(8), P. e3002796 - e3002796

Published: Aug. 29, 2024

Mobile genetic elements shape microbial gene repertoires and populations. Recent results reveal that many, possibly most, mobile require helpers to transfer between genomes, which we refer as Hitcher Genetic Elements (hitchers or HGEs). They may be a large fraction of pathogenicity resistance genomic islands, whose mechanisms have remained enigmatic for decades. Together with their helper bacterial hosts, hitchers form tripartite networks interactions evolve rapidly within parasitism–mutualism continuum. In this emerging view genomes communities many questions arise. Which are being moved, by whom, how? How often costly hyper-parasites beneficial mutualists? What is the evolutionary origin hitchers? Are there key advantages associated hitchers’ lifestyle justify unexpected abundance? And why systematically smaller than helpers? essay, start answering these point ways ahead understanding principles, origin, mechanisms, impact in ecology evolution.

Language: Английский

Citations

10
Interactions and evolutionary relationships among bacterial mobile genetic elements DOI
Andrew S. Lang, Alison Buchan, Vincent Burrus

et al.

Nature Reviews Microbiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 11, 2025

Language: Английский

Citations

1
Going viral: The role of mobile genetic elements in bacterial immunity DOI
Beatriz Beamud, Fabienne Benz,

David Bikard

et al.

Cell Host & Microbe, Journal Year: 2024, Volume and Issue: 32(6), P. 804 - 819

Published: June 1, 2024

Language: Английский

Citations

8
Non-Canonical Aspects of Antibiotics and Antibiotic Resistance DOI Creative Commons
Carlos F. Amábile-Cuevas,

Sofia Lund-Zaina

Antibiotics, Journal Year: 2024, Volume and Issue: 13(6), P. 565 - 565

Published: June 17, 2024

The understanding of antibiotic resistance, one the major health threats our time, is mostly based on dated and incomplete notions, especially in clinical contexts. “canonical” mechanisms action pharmacodynamics antibiotics, as well methods used to assess their activity upon bacteria, have not changed decades; same applies definition, acquisition, selective pressures, drivers resistance. As a consequence, strategies improve usage overcome resistance ultimately failed. This review gathers most “non-canonical” notions antibiotics resistance: from alternative limitations susceptibility testing wide variety lateral gene transfer mechanisms, ubiquity, societal factors maintaining Only by having “big picture” view problem can adequate harness be devised. These must global, addressing many aspects that drive increasing prevalence resistant bacteria aside use antibiotics.

Language: Английский

Citations

4
Mobile Integrons Encode Phage Defense Systems DOI Creative Commons
Nicolas Kieffer, Alberto Hipólito, Laura Ortiz-Miravalles

et al.

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

Published: July 2, 2024

Abstract Integrons are bacterial genetic elements that capture, stockpile and modulate the expression of genes encoded in integron cassettes. Mobile (MI) borne on plasmids, acting as a vehicle for hundreds antimicrobial resistance among key pathogens. These also carry g ene c assettes u nknown function ( gcu s) whose role adaptive value remains unexplored. Here we show s encode phage systems, many which novel. B acteriophage r esistance i ntegron (BRiCs) can be combined mixed with cassettes to produce multiphage or drug/phage-resistance. The fitness costs BRiCs variable, dependent context, modulated by changing order array. Hence, MIs act highly mobile, low-cost defense islands. Figure Summary Novel systems identified Integrons. We confronted unknown from mobile integrons against panel phage. characterized 13 Bacteriophage Resistance Cassettes confirmed their Klebsiella pneumoniae Pseudomonas aeruginosa . Combined other cassettes, multi-phage/antibiotic resistance. Additionally, cost reduced an

Language: Английский

Citations

2
Belt and braces: Two escape ways to maintain the cassette reservoir of large chromosomal integrons DOI Creative Commons
Egill Richard, Baptiste Darracq, Eloi Littner

et al.

PLoS Genetics, Journal Year: 2024, Volume and Issue: 20(4), P. e1011231 - e1011231

Published: April 5, 2024

Integrons are adaptive devices that capture, stockpile, shuffle and express gene cassettes thereby sampling combinatorial phenotypic diversity. Some integrons called sedentary chromosomal (SCIs) can be massive structures containing hundreds of cassettes. Since most these non-expressed, it is not clear how they remain stable over long evolutionary timescales. Recently, was found the experimental inversion SCI Vibrio cholerae led to a dramatic increase cassette excision rate associated with fitness defect. Here, we question sustainability this apparently counter selected genetic context. Through evolution, find integrase rapidly inactivated inverted recover its original orientation by homologous recombination between two insertion sequences (ISs) present in array. These outcomes restore normal growth prevent loss cassettes, enabling SCIs retain their roles as reservoirs functions. results illustrate nice interplay orientation, genome rearrangement, bacterial demonstrate benefit from embedded ISs.

Language: Английский

Citations

1
Redefining the bacteriophage mv4 site‐specific recombination system and the sequence specificity of its attB and core‐attP sites DOI
Kevin Debatisse, Pierre Lopez,

Maryse Poli

et al.

Molecular Microbiology, Journal Year: 2024, Volume and Issue: 121(6), P. 1200 - 1216

Published: May 5, 2024

Abstract Through their involvement in the integration and excision of a large number mobile genetic elements, such as phages integrative conjugative elements (ICEs), site‐specific recombination systems based on heterobivalent tyrosine recombinases play major role genome dynamics evolution. However, despite hundreds these having been identified databases, very few have described detail, with none from that infect Bacillota (formerly Firmicutes ). In this study, we reanalyzed module Lactobacillus delbrueckii subsp. bulgaricus phage mv4, previously considered atypical compared classical systems. Our results reveal mv4 integrase is 369 aa protein all structural hallmarks Tn 916 family it cooperatively interacts its sites. Using randomized DNA libraries, NGS sequencing, other molecular approaches, show 21‐bp core‐ attP attB sites similarities to only if considering nucleotide degeneracy, two 7‐bp inverted regions corresponding Int core‐binding surrounding strand‐exchange region. We also examined different compositional constraints regions, which define sequence space permissible

Language: Английский

Citations

1
The recombination efficiency of the bacterial integron depends on the mechanical stability of the synaptic complex DOI Creative Commons
Ekaterina Vorobevskaia, Céline Loot, Didier Mazel

et al.

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

Published: April 13, 2024

Abstract The predominant tool for adaptation in Gram-negative bacteria is a genetic system called integron. Under conditions of stress, it rearranges gene cassettes, ensuring their sampling through expression, to offer solution overcoming the initial stress. Integrons are major actor multiple antibiotic resistances, recognized global health threat. Cassettes recombined by unique recombination process involving tyrosine recombinase – IntI integrase and folded single-stranded DNA hairpins attC sites which terminate each cassette. Four recombinases two form macromolecular synaptic complex, key focus our study. bottom strand all shows highest efficiency vivo than top one, however, still varies several orders magnitude underlying reason remains unclear. Here, we established an optical tweezers force-spectroscopy assay that allows us probe complex stability. We found seven combinations great variability mechanical Two protein variants also showed strong influence on then determined efficiencies different site discovered correlation between stability indicating regulatory mechanism from sequence Taking into account known forces during metabolism, suggest variation mediated strongly

Language: Английский

Citations

0
Integrons: Genetic Dynamic Elements in Aeromonas DOI Creative Commons
Rogelio Rojas-Rios, Everardo Curiel‐Quesada, Abigail Pérez‐Valdespino

et al.

IntechOpen eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: June 13, 2024

Integrons are genetic elements able to incorporate, express, and exchange cassettes. Cassette exchanges mediated by an integrase that excises reinserts them via site-specific recombination between flanking att sequences. Cassettes lack for the most part a promoter, their excision reinsertion at attI site, downstream Pc render transcriptionally active. This work documents occurrence of complete integrons or parts in Aeromonas examines dynamics these elements. Class 1 linked antibiotic-resistant cassettes were abundant strains isolated from environmental clinical samples. Detection class 2 3 was infrequent. Only one report 4-like integron sp. genomospecies paramedia found, but search genomes revealed second after those belonging 1. In addition integrons, clusters attC sites lacking neighboring integron-integrase (CALINs), single (SALINs), orphan genes found chromosomes, low percentage plasmids. Concerning behavior, it is known be regulated SOS response could also controlled host specific factors.

Language: Английский

Citations

0
The recombination efficiency of the bacterial integron depends on the mechanical stability of the synaptic complex DOI Creative Commons
Ekaterina Vorobevskaia, Céline Loot, Didier Mazel

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(50)

Published: Dec. 13, 2024

Multiple antibiotic resistances are a major global health threat. The predominant tool for adaptation in Gram-negative bacteria is the integron. Under stress, it rearranges gene cassettes to offer an escape using tyrosine recombinase IntI, recognizing folded DNA hairpins, attC sites. Four recombinases and two sites form synaptic complex. Yet, unclear reasons, recombination efficiency varies greatly. Here, we established optical tweezers force spectroscopy assay probe complex stability revealed, seven combinations of sites, significant variability mechanical stability. We found strong correlation between vivo, indicating regulatory mechanism from structure macromolecular Taking into account known forces during metabolism, propose that variation integron vivo mediated by anticipate further processes also affected their corresponding

Language: Английский

Citations

0