Dataset Information

A Bioinformatic Analysis of Integrative Mobile Genetic Elements Highlights Their Role in Bacterial Adaptation.

ABSTRACT: Mobile genetic elements (MGEs) contribute to bacterial adaptation and evolution; however, high-throughput, unbiased MGE detection remains challenging. We describe MGEfinder, a bioinformatic toolbox that identifies integrative MGEs and their insertion sites by using short-read sequencing data. MGEfinder identifies the genomic site of each MGE insertion and infers the identity of the inserted sequence. We apply MGEfinder to 12,374 sequenced isolates of 9 prevalent bacterial pathogens, including Mycobacterium tuberculosis, Staphylococcus aureus, and Escherichia coli, and identify thousands of MGEs, including candidate insertion sequences, conjugative transposons, and prophage elements. The MGE repertoire and insertion rates vary across species, and integration sites often cluster near genes related to antibiotic resistance, virulence, and pathogenicity. MGE insertions likely contribute to antibiotic resistance in laboratory experiments and clinical isolates. Additionally, we identified thousands of mobility genes, a subset of which have unknown function opening avenues for exploration. Future application of MGEfinder to commensal bacteria will further illuminate bacterial adaptation and evolution.

SUBMITTER: Durrant MG

PROVIDER: S-EPMC6952549 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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A Bioinformatic Analysis of Integrative Mobile Genetic Elements Highlights Their Role in Bacterial Adaptation.

Durrant Matthew G MG Li Michelle M MM Siranosian Benjamin A BA Montgomery Stephen B SB Bhatt Ami S AS

Cell host & microbe 20191217 1

Mobile genetic elements (MGEs) contribute to bacterial adaptation and evolution; however, high-throughput, unbiased MGE detection remains challenging. We describe MGEfinder, a bioinformatic toolbox that identifies integrative MGEs and their insertion sites by using short-read sequencing data. MGEfinder identifies the genomic site of each MGE insertion and infers the identity of the inserted sequence. We apply MGEfinder to 12,374 sequenced isolates of 9 prevalent bacterial pathogens, including My ...[more]

PMID: 31862382

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Project description:Methicillin-resistant Staphylococcus aureus (MRSA) clonal-complex 398 (CC398) is the dominant livestock-associated (LA) MRSA lineage in European livestock and an increasing cause of difficult-to-treat human disease. LA-CC398 MRSA evolved from a diverse human-associated methicillin-sensitive population, and this transition from humans to livestock was associated with three mobile genetic elements (MGEs). In this study, we apply transposon-directed insertion site sequencing (TraDIS), a high-throughput transposon mutagenesis approach, to investigate genetic signatures that contribute to LA-CC398 causing disease in humans. We identified 26 genes associated with LA-CC398 survival in human blood and 47 genes in porcine blood. We carried out phylogenetic reconstruction on 1,180 CC398 isolates to investigate the genetic context of all identified genes. We found that all genes associated with survival in human blood were part of the CC398 core genome, while 2/47 genes essential for survival in porcine blood were located on MGEs. Gene SAPIG0966 was located on the previously identified Tn916 transposon carrying a tetracycline resistance gene, which has been shown to be stably inherited within LA-CC398. Gene SAPIG1525 was carried on a phage element, which in part, matched phiSa2wa_st1, a previously identified bacteriophage carrying the Panton-Valentine leucocidin (PVL) virulence factor. Gene deletion mutants constructed in two LA-CC398 strains confirmed that the SAPIG0966 carrying Tn916 and SAPIG1525 were important for CC398 survival in porcine blood. Our study shows that MGEs that carry antimicrobial resistance and virulence genes could have a secondary function in bacterial survival in blood and may be important for host adaptation. IMPORTANCE CC398 is the dominant type of methicillin-resistant Staphylococcus aureus (MRSA) in European livestock and a growing cause of human infections. Previous studies have suggested MRSA CC398 evolved from human-associated methicillin-sensitive Staphylococcus aureus and is capable of rapidly readapting to human hosts while maintaining antibiotic resistance. Using high-throughput transposon mutagenesis, our study identified 26 and 47 genes important for MRSA CC398 survival in human and porcine blood, respectively. Two of the genes important for MRSA CC398 survival in porcine blood were located on mobile genetic elements (MGEs) carrying resistance or virulence genes. Our study shows that these MGEs carrying antimicrobial resistance and virulence genes could have a secondary function in bacterial survival in blood and may be important for blood infection and host adaptation.

Dataset Information

A Bioinformatic Analysis of Integrative Mobile Genetic Elements Highlights Their Role in Bacterial Adaptation.

Publications

A Bioinformatic Analysis of Integrative Mobile Genetic Elements Highlights Their Role in Bacterial Adaptation.

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