Chromosomal Integrons are Genetically and Functionally Isolated Units of Genomes
Paula Blanco,
Filipa Trig da Roza,
Laura Toribio-Celestino
et al.
Abstract:Integrons are genetic elements that increase the evolvability of bacteria by capturing new genes and stockpiling them in arrays. Sedentary chromosomal integrons (SCIs), can be massive and highly stabilized structures encoding hundreds of genes, whose function remains generally unknown. SCIs have co-evolved with the host for aeons and are highly intertwined with their physiology from a mechanistic point of view. But, paradoxically, other aspects, like their variable content and location within the genome, sugge… Show more
“…An extreme case of this is shown by Darracq et al in a back-to-back paper in this issue, where they describe the presence of PICs in the Superintegron of Vibrio cholerae. Indeed, in a recent work we have shown that the Superintegron is carried at no measurable cost 59 . Additionally, their findings proves that chromosomal integrons are virtually infinite repositories of PICs from where they can be recollected by mobile integrons.…”
Integrons are bacterial genetic elements that capture, stockpile and modulate the expression of genes encoded in integron cassettes. Mobile Integrons (MI) are borne on plasmids, acting as a vehicle for hundreds of antimicrobial resistance genes among key pathogens. These elements also carrygenecassettes ofunknown function (gcus) whose role and adaptive value remains unexplored. Recent years have witnessed the discovery of a myriad defence systems against bacteriophages, highlighting that viral infection is a major selective pressure for bacteria. We hence sought to explore ifgcus could encode phage defence systems. Using the INTEGRALL database, we established a collection of 129gcus in pMBA, a vector where cassettes are established as part of a class 1 integron. PADLOC and DefenseFinder predicted four phage defence systems in this collection, comprising Lamassu, CBASS and two ABI (abortive infection) systems. We experimentally challenged all cassettes with phages and found nine additional candidates that were not detectedin silico. We have characterized in depth the 13gcus against a panel of phages inEscherichia coliconfirming their role asphage defence integroncassettes (PICs). We used recombination assays to verify that all systems arebona fideintegron cassettes and are therefore mobile. We show that PICs confer resistance in other clinically relevant species, such asKlebsiella pneumoniaeandPseudomonas aeruginosa.Several PICs also limit prophage activation, providing protection at the population-level. Given the stockpiling capacity of integrons, we explored the additivity of phenotypes and found that integrons with two PICs confer multiphage-resistance. Additionally, when combined with antimicrobial resistance genes, integrons confer simultaneously drug and phage resistance. Crucially, we also show that the position of apicin the array can strongly decrease its cost. Our results prove a role of integrons in phage defence, acting as highly mobile, low-cost defence islands. This has important implications in the spread of defence systems, and on the future of phage therapy.
“…An extreme case of this is shown by Darracq et al in a back-to-back paper in this issue, where they describe the presence of PICs in the Superintegron of Vibrio cholerae. Indeed, in a recent work we have shown that the Superintegron is carried at no measurable cost 59 . Additionally, their findings proves that chromosomal integrons are virtually infinite repositories of PICs from where they can be recollected by mobile integrons.…”
Integrons are bacterial genetic elements that capture, stockpile and modulate the expression of genes encoded in integron cassettes. Mobile Integrons (MI) are borne on plasmids, acting as a vehicle for hundreds of antimicrobial resistance genes among key pathogens. These elements also carrygenecassettes ofunknown function (gcus) whose role and adaptive value remains unexplored. Recent years have witnessed the discovery of a myriad defence systems against bacteriophages, highlighting that viral infection is a major selective pressure for bacteria. We hence sought to explore ifgcus could encode phage defence systems. Using the INTEGRALL database, we established a collection of 129gcus in pMBA, a vector where cassettes are established as part of a class 1 integron. PADLOC and DefenseFinder predicted four phage defence systems in this collection, comprising Lamassu, CBASS and two ABI (abortive infection) systems. We experimentally challenged all cassettes with phages and found nine additional candidates that were not detectedin silico. We have characterized in depth the 13gcus against a panel of phages inEscherichia coliconfirming their role asphage defence integroncassettes (PICs). We used recombination assays to verify that all systems arebona fideintegron cassettes and are therefore mobile. We show that PICs confer resistance in other clinically relevant species, such asKlebsiella pneumoniaeandPseudomonas aeruginosa.Several PICs also limit prophage activation, providing protection at the population-level. Given the stockpiling capacity of integrons, we explored the additivity of phenotypes and found that integrons with two PICs confer multiphage-resistance. Additionally, when combined with antimicrobial resistance genes, integrons confer simultaneously drug and phage resistance. Crucially, we also show that the position of apicin the array can strongly decrease its cost. Our results prove a role of integrons in phage defence, acting as highly mobile, low-cost defence islands. This has important implications in the spread of defence systems, and on the future of phage therapy.
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