The Association between Insertion Sequences and Antibiotic Resistance Genes

ABSTRACT Insertion sequences (ISs) are abundant mobile genetic elements on bacterial genomes, responsible for mobilization of many genes, including antibiotic resistance genes (ARGs). As ARGs often occur in similar genetic contexts, understanding which ISs tend to be associated with known ARGs could...

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Autores principales:	Mohammad Razavi, Erik Kristiansson, Carl-Fredrik Flach, D. G. Joakim Larsson
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	antibiotic resistance bacterial genomes environment insertion sequences metagenomics resistome Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/dfd517ae66f5443bb4f522a6a1340432
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spelling	oai:doaj.org-article:dfd517ae66f5443bb4f522a6a13404322021-11-15T15:30:58ZThe Association between Insertion Sequences and Antibiotic Resistance Genes10.1128/mSphere.00418-202379-5042https://doaj.org/article/dfd517ae66f5443bb4f522a6a13404322020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00418-20https://doaj.org/toc/2379-5042ABSTRACT Insertion sequences (ISs) are abundant mobile genetic elements on bacterial genomes, responsible for mobilization of many genes, including antibiotic resistance genes (ARGs). As ARGs often occur in similar genetic contexts, understanding which ISs tend to be associated with known ARGs could be a first step toward discovering novel ARGs through predictive or experimental strategies. This could be valuable, as early identification of ARGs in pathogens could facilitate surveillance, confinement actions, molecular diagnostics, and drug development. Here, we present a comprehensive analysis of the association of specific ISs with known ARGs. A large collection of bacterial genomes was used to characterize the immediate context of 2,437 known ARGs and 3,768 ISs. While many ARGs were consistently found close to specific ISs, the contexts around all ISs were more variable. Nevertheless, a subset of individual ISs, as well as tentative composite transposons, showed significant associations with ARGs. These included, e.g., insertion sequences classified as IS6, Tn3, IS4, and IS1 that were not only strongly associated with diverse ARGs but also highly abundant in pathogens. Therefore, we conclude that the context of this subset of ISs and tentative composite transposons would be particularly valuable to discover novel ARGs through modeling or empirical approaches. A set of 1,891 metagenomes were analyzed to identify environments where those ISs commonly associated with ARGs were particularly abundant. The associations found in metagenomes were similar to those found in genomes. IMPORTANCE The emergence and spread of antibiotic resistance genes (ARGs) among pathogens threaten the prevention and treatment of bacterial infections as well as our food production chains. Early knowledge about mobile ARGs that are present in pathogens or that have the potential to become clinically relevant could help mitigate potential negative consequences. Recently, exploring integron gene cassettes was shown to be successful for identifying novel mobilized ARGs, some of which were already circulating in pathogens. Still, only a subset of ARGs is mobilized by integrons, and the contexts of other mobile genetic elements associated with ARGs remain unexplored. This includes insertion sequences (ISs) responsible for the mobilization of many ARGs. Our analyses identified ISs, species, and environments where ARG-IS relationships are particularly strong. This could be a first step to guide the discovery of novel ARGs, while also providing insights into mechanisms involved in the mobilization and transfer of ARGs.Mohammad RazaviErik KristianssonCarl-Fredrik FlachD. G. Joakim LarssonAmerican Society for Microbiologyarticleantibiotic resistancebacterial genomesenvironmentinsertion sequencesmetagenomicsresistomeMicrobiologyQR1-502ENmSphere, Vol 5, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	antibiotic resistance bacterial genomes environment insertion sequences metagenomics resistome Microbiology QR1-502
spellingShingle	antibiotic resistance bacterial genomes environment insertion sequences metagenomics resistome Microbiology QR1-502 Mohammad Razavi Erik Kristiansson Carl-Fredrik Flach D. G. Joakim Larsson The Association between Insertion Sequences and Antibiotic Resistance Genes
description	ABSTRACT Insertion sequences (ISs) are abundant mobile genetic elements on bacterial genomes, responsible for mobilization of many genes, including antibiotic resistance genes (ARGs). As ARGs often occur in similar genetic contexts, understanding which ISs tend to be associated with known ARGs could be a first step toward discovering novel ARGs through predictive or experimental strategies. This could be valuable, as early identification of ARGs in pathogens could facilitate surveillance, confinement actions, molecular diagnostics, and drug development. Here, we present a comprehensive analysis of the association of specific ISs with known ARGs. A large collection of bacterial genomes was used to characterize the immediate context of 2,437 known ARGs and 3,768 ISs. While many ARGs were consistently found close to specific ISs, the contexts around all ISs were more variable. Nevertheless, a subset of individual ISs, as well as tentative composite transposons, showed significant associations with ARGs. These included, e.g., insertion sequences classified as IS6, Tn3, IS4, and IS1 that were not only strongly associated with diverse ARGs but also highly abundant in pathogens. Therefore, we conclude that the context of this subset of ISs and tentative composite transposons would be particularly valuable to discover novel ARGs through modeling or empirical approaches. A set of 1,891 metagenomes were analyzed to identify environments where those ISs commonly associated with ARGs were particularly abundant. The associations found in metagenomes were similar to those found in genomes. IMPORTANCE The emergence and spread of antibiotic resistance genes (ARGs) among pathogens threaten the prevention and treatment of bacterial infections as well as our food production chains. Early knowledge about mobile ARGs that are present in pathogens or that have the potential to become clinically relevant could help mitigate potential negative consequences. Recently, exploring integron gene cassettes was shown to be successful for identifying novel mobilized ARGs, some of which were already circulating in pathogens. Still, only a subset of ARGs is mobilized by integrons, and the contexts of other mobile genetic elements associated with ARGs remain unexplored. This includes insertion sequences (ISs) responsible for the mobilization of many ARGs. Our analyses identified ISs, species, and environments where ARG-IS relationships are particularly strong. This could be a first step to guide the discovery of novel ARGs, while also providing insights into mechanisms involved in the mobilization and transfer of ARGs.
format	article
author	Mohammad Razavi Erik Kristiansson Carl-Fredrik Flach D. G. Joakim Larsson
author_facet	Mohammad Razavi Erik Kristiansson Carl-Fredrik Flach D. G. Joakim Larsson
author_sort	Mohammad Razavi
title	The Association between Insertion Sequences and Antibiotic Resistance Genes
title_short	The Association between Insertion Sequences and Antibiotic Resistance Genes
title_full	The Association between Insertion Sequences and Antibiotic Resistance Genes
title_fullStr	The Association between Insertion Sequences and Antibiotic Resistance Genes
title_full_unstemmed	The Association between Insertion Sequences and Antibiotic Resistance Genes
title_sort	association between insertion sequences and antibiotic resistance genes
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/dfd517ae66f5443bb4f522a6a1340432
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The Association between Insertion Sequences and Antibiotic Resistance Genes

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