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Analysis of the resistome of a multidrug-resistant NDM-1-producing Escherichia coli strain by high-throughput genome sequencing.

ABSTRACT: The resistome of the multidrug-resistant Escherichia coli strain 271 carrying the plasmid-mediated bla(NDM-1) carbapenemase gene was analyzed by high-throughput genome sequencing. The p271A plasmid carrying the bla(NDM-1) gene was 35.9 kb in size and possessed an IncN-type backbone that harbored a novel replicase gene. Acquisition of the bla(NDM-1) gene on plasmid p271A had been likely the result of a cointegration event involving the transposase of Tn5403. The expression of bla(NDM-1) was associated with the insertion sequence ISAba125 likely originating from Acinetobacter baumannii. E. coli 271 accumulated multiple resistance determinants, including five ?-lactamase genes (comprising the extended-spectrum ?-lactamase CTX-M-15), two 16S RNA methylase ArmA- and RmtB-encoding genes, and the qepA gene encoding an efflux pump involved in resistance to fluoroquinolones. These resistance genes were located on three additional plasmids, of 160 kb (IncA/C), 130 kb (IncF), and 110 kb (IncI1). In addition, several chromosomally encoded resistance determinants were identified, such as topoisomerase mutations, porin modifications and truncations, and the intrinsic ampC gene of E. coli that was weakly expressed. The multidrug resistance pattern observed for E. coli 271 was therefore the result of combined chromosome- and plasmid-encoded mechanisms.

SUBMITTER: Poirel L

PROVIDER: S-EPMC3165296 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Analysis of the resistome of a multidrug-resistant NDM-1-producing Escherichia coli strain by high-throughput genome sequencing.

Poirel Laurent L Bonnin Rémy A RA Nordmann Patrice P

Antimicrobial agents and chemotherapy 20110711 9

The resistome of the multidrug-resistant Escherichia coli strain 271 carrying the plasmid-mediated bla(NDM-1) carbapenemase gene was analyzed by high-throughput genome sequencing. The p271A plasmid carrying the bla(NDM-1) gene was 35.9 kb in size and possessed an IncN-type backbone that harbored a novel replicase gene. Acquisition of the bla(NDM-1) gene on plasmid p271A had been likely the result of a cointegration event involving the transposase of Tn5403. The expression of bla(NDM-1) was assoc ...[more]

PMID: 21746951

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Project description:Escherichia coli ST131 is a globally disseminated, multidrug resistant clone responsible for a high proportion of urinary tract and bloodstream infections. The rapid emergence and successful spread of E. coli ST131 is strongly associated with antibiotic resistance; however, this phenotype alone is unlikely to explain its dominance amongst multidrug resistant uropathogens circulating worldwide in hospitals and the community. Thus, a greater understanding of the molecular mechanisms that underpin the fitness of E. coli ST131 is required. In this study, we employed hyper-saturated transposon mutagenesis in combination with multiplexed transposon directed insertion-site sequencing to define the essential genes required for in vitro growth and the serum resistome (i.e. genes required for resistance to human serum) of E. coli EC958, a representative of the predominant E. coli ST131 clonal lineage. We identified 315 essential genes in E. coli EC958, 231 (73%) of which were also essential in E. coli K-12. The serum resistome comprised 56 genes, the majority of which encode membrane proteins or factors involved in lipopolysaccharide (LPS) biosynthesis. Targeted mutagenesis confirmed a role in serum resistance for 46 (82%) of these genes. The murein lipoprotein Lpp, along with two lipid A-core biosynthesis enzymes WaaP and WaaG, were most strongly associated with serum resistance. While LPS was the main resistance mechanism defined for E. coli EC958 in serum, the enterobacterial common antigen and colanic acid also impacted on this phenotype. Our analysis also identified a novel function for two genes, hyxA and hyxR, as minor regulators of O-antigen chain length. This study offers novel insight into the genetic make-up of E. coli ST131, and provides a framework for future research on E. coli and other Gram-negative pathogens to define their essential gene repertoire and to dissect the molecular mechanisms that enable them to survive in the bloodstream and cause disease.

Dataset Information

Analysis of the resistome of a multidrug-resistant NDM-1-producing Escherichia coli strain by high-throughput genome sequencing.

Publications

Analysis of the resistome of a multidrug-resistant NDM-1-producing Escherichia coli strain by high-throughput genome sequencing.

Similar Datasets

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