Integron activity accelerates the evolution of antibiotic resistance

Souque, Célia; Escudero, José Antonio; MacLean, R. Craig

doi:10.7554/elife.62474

Cited by 61 publications

(64 citation statements)

References 76 publications

(61 reference statements)

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“…Activity of the integrase allows: (i) modulation of cassette expression, (ii) rapid gain of additional copies of selected cassettes and (iii) elimination of redundant cassettes. Integrase activity does not compromise genome integrity due to the high specificity of integrase-mediated recombination [32][33][34]. Thus, integrase-mediated cassette re-shuffling in stressful environments could accelerate bacterial evolution allowing bacteria to optimize cassette expression and maximize fitness.…”

Section: Mobile Genetic Elementsmentioning

confidence: 99%

The Escherichia coli SOS Response: Much More than DNA Damage Repair

Podlesek¹,

Bertok²

2023

Escherichia Coli - Old and New Insights

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The Escherichia coli SOS response is an inducible DNA damage repair pathway controlled by two key regulators, LexA, a repressor and RecA, an inducer. Upon DNA damage RecA is activated and stimulates self cleavage of LexA, leading to, in E. coli, derepresion of approximately 50 SOS genes. The response is triggered by exogenous and endogenous signals that bacteria encounter at a number of sites within the host. Nevertheless, besides regulating DNA damage repair the SOS response plays a much broader role. Thus, SOS error prone polymerases promote elevated mutation rates significant for genetic adaptation and diversity, including antibiotic resistance. Here we review the E. coli SOS response in relation to recalcitrance to antimicrobials, including persister and biofilm formation, horizontal gene tranfer, gene mobility, bacterial pathogenicity, as well SOS induced bacteriocins that drive diversification. Phenotypic heterogeneity in expression of the SOS regulator genes, recA and lexA as well as colicin activity genes is also discussed.

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Section: Mobile Genetic Elementsmentioning

confidence: 99%

The Escherichia coli SOS Response: Much More than DNA Damage Repair

Podlesek¹,

Bertok²

2023

Escherichia Coli - Old and New Insights

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“…The strength of cassette expression decreases with distance from the promoter [3]. During SOS-inducing stress, intI1 expression is upregulated, leading to the acquisition of novel gene cassettes and rearrangement of existing cassettes, such that incoming cassettes are inserted at the start of the array where their expression is maximised [52,53]. Lineages with first-position cassettes that confer significant advantages are therefore likely to be selected.…”

Section: Ongoing Integron-driven Evolution In the Anthropocenementioning

confidence: 99%

The Natural History of Integrons

et al. 2021

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Integrons were first identified because of their central role in assembling and disseminating antibiotic resistance genes in commensal and pathogenic bacteria. However, these clinically relevant integrons represent only a small proportion of integron diversity. Integrons are now known to be ancient genetic elements that are hotspots for genomic diversity, helping to generate adaptive phenotypes. This perspective examines the diversity, functions, and activities of integrons within both natural and clinical environments. We show how the fundamental properties of integrons exquisitely pre-adapted them to respond to the selection pressures imposed by the human use of antimicrobial compounds. We then follow the extraordinary increase in abundance of one class of integrons (class 1) that has resulted from its acquisition by multiple mobile genetic elements, and subsequent colonisation of diverse bacterial species, and a wide range of animal hosts. Consequently, this class of integrons has become a significant pollutant in its own right, to the extent that it can now be detected in most ecosystems. As human activities continue to drive environmental instability, integrons will likely continue to play key roles in bacterial adaptation in both natural and clinical settings. Understanding the ecological and evolutionary dynamics of integrons can help us predict and shape these outcomes that have direct relevance to human and ecosystem health.

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“…Nevertheless, both "variants" of pESI-like included integrons associated to different AMR genes. Indeed, the presence of these genetic elements has recently demonstrated to accelerate the evolution from susceptible to resistant microorganisms (Souque, et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Evidence of structural rearrangements and variability in pESI(like) megaplasmids of S.Infantis by resolving the pESI-like ESBL-producing variants

Alba

Carfora

Feltrin

et al. 2021

Preprint

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The increasing prevalence of pESI(like)-positive, multidrug-resistant (MDR) S. Infantis in Europe is a cause of major concern. As previously demonstrated, the pESI(like) megaplasmid is not only a carrier of antimicrobial resistant (AMR) genes (at least tet, dfr and sul genes), but also harbours several virulence factors and toxin/antitoxin systems that enhance its persistence in the S. Infantis host. In this study, five pESI(like) plasmids were long-read sequenced using Oxford Nanopore Technology (ONT) and their complete sequences were resolved. Comparison of the structure and gene content of the five sequenced plasmids, and further comparison with previously published pESI(like) sequences, indicated that although the sequence of pESI(like) remains almost identical, its structure is composed of regions inserted or transposed after different events. The results obtained in this study are essential to better understand the plasticity and the evolution of the pESI(like) megaplasmid, and therefore to better address risk management options and policy decisions to fight against AMR and MDR in Salmonella and other food-borne pathogens.

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Integron activity accelerates the evolution of antibiotic resistance

Cited by 61 publications

References 76 publications

The Escherichia coli SOS Response: Much More than DNA Damage Repair

The Escherichia coli SOS Response: Much More than DNA Damage Repair

The Natural History of Integrons

Evidence of structural rearrangements and variability in pESI(like) megaplasmids of S.Infantis by resolving the pESI-like ESBL-producing variants

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