Comprehensive Genome Analysis of Carbapenemase-Producing <italic toggle="yes">Enterobacter</italic> spp.: New Insights into Phylogeny, Population Structure, and Resistance Mechanisms

ABSTRACT Knowledge regarding the genomic structure of Enterobacter spp., the second most prevalent carbapenemase-producing Enterobacteriaceae, remains limited. Here we sequenced 97 clinical Enterobacter species isolates that were both carbapenem susceptible and resistant from various geographic regi...

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Autores principales:	Kalyan D. Chavda, Liang Chen, Derrick E. Fouts, Granger Sutton, Lauren Brinkac, Stephen G. Jenkins, Robert A. Bonomo, Mark D. Adams, Barry N. Kreiswirth
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Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/5929499c28984899965978be8bf2cb94
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spelling	oai:doaj.org-article:5929499c28984899965978be8bf2cb942021-11-15T15:50:15ZComprehensive Genome Analysis of Carbapenemase-Producing <italic toggle="yes">Enterobacter</italic> spp.: New Insights into Phylogeny, Population Structure, and Resistance Mechanisms10.1128/mBio.02093-162150-7511https://doaj.org/article/5929499c28984899965978be8bf2cb942016-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02093-16https://doaj.org/toc/2150-7511ABSTRACT Knowledge regarding the genomic structure of Enterobacter spp., the second most prevalent carbapenemase-producing Enterobacteriaceae, remains limited. Here we sequenced 97 clinical Enterobacter species isolates that were both carbapenem susceptible and resistant from various geographic regions to decipher the molecular origins of carbapenem resistance and to understand the changing phylogeny of these emerging and drug-resistant pathogens. Of the carbapenem-resistant isolates, 30 possessed blaKPC-2, 40 had blaKPC-3, 2 had blaKPC-4, and 2 had blaNDM-1. Twenty-three isolates were carbapenem susceptible. Six genomes were sequenced to completion, and their sizes ranged from 4.6 to 5.1 Mbp. Phylogenomic analysis placed 96 of these genomes, 351 additional Enterobacter genomes downloaded from NCBI GenBank, and six newly sequenced type strains into 19 phylogenomic groups—18 groups (A to R) in the Enterobacter cloacae complex and Enterobacter aerogenes. Diverse mechanisms underlying the molecular evolutionary trajectory of these drug-resistant Enterobacter spp. were revealed, including the acquisition of an antibiotic resistance plasmid, followed by clonal spread, horizontal transfer of blaKPC-harboring plasmids between different phylogenomic groups, and repeated transposition of the blaKPC gene among different plasmid backbones. Group A, which comprises multilocus sequence type 171 (ST171), was the most commonly identified (23% of isolates). Genomic analysis showed that ST171 isolates evolved from a common ancestor and formed two different major clusters; each acquiring unique blaKPC-harboring plasmids, followed by clonal expansion. The data presented here represent the first comprehensive study of phylogenomic interrogation and the relationship between antibiotic resistance and plasmid discrimination among carbapenem-resistant Enterobacter spp., demonstrating the genetic diversity and complexity of the molecular mechanisms driving antibiotic resistance in this genus. IMPORTANCE Enterobacter spp., especially carbapenemase-producing Enterobacter spp., have emerged as a clinically significant cause of nosocomial infections. However, only limited information is available on the distribution of carbapenem resistance across this genus. Augmenting this problem is an erroneous identification of Enterobacter strains because of ambiguous typing methods and imprecise taxonomy. In this study, we used a whole-genome-based comparative phylogenetic approach to (i) revisit and redefine the genus Enterobacter and (ii) unravel the emergence and evolution of the Klebsiella pneumoniae carbapenemase-harboring Enterobacter spp. Using genomic analysis of 447 sequenced strains, we developed an improved understanding of the species designations within this complex genus and identified the diverse mechanisms driving the molecular evolution of carbapenem resistance. The findings in this study provide a solid genomic framework that will serve as an important resource in the future development of molecular diagnostics and in supporting drug discovery programs.Kalyan D. ChavdaLiang ChenDerrick E. FoutsGranger SuttonLauren BrinkacStephen G. JenkinsRobert A. BonomoMark D. AdamsBarry N. KreiswirthAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 6 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Kalyan D. Chavda Liang Chen Derrick E. Fouts Granger Sutton Lauren Brinkac Stephen G. Jenkins Robert A. Bonomo Mark D. Adams Barry N. Kreiswirth Comprehensive Genome Analysis of Carbapenemase-Producing <italic toggle="yes">Enterobacter</italic> spp.: New Insights into Phylogeny, Population Structure, and Resistance Mechanisms
description	ABSTRACT Knowledge regarding the genomic structure of Enterobacter spp., the second most prevalent carbapenemase-producing Enterobacteriaceae, remains limited. Here we sequenced 97 clinical Enterobacter species isolates that were both carbapenem susceptible and resistant from various geographic regions to decipher the molecular origins of carbapenem resistance and to understand the changing phylogeny of these emerging and drug-resistant pathogens. Of the carbapenem-resistant isolates, 30 possessed blaKPC-2, 40 had blaKPC-3, 2 had blaKPC-4, and 2 had blaNDM-1. Twenty-three isolates were carbapenem susceptible. Six genomes were sequenced to completion, and their sizes ranged from 4.6 to 5.1 Mbp. Phylogenomic analysis placed 96 of these genomes, 351 additional Enterobacter genomes downloaded from NCBI GenBank, and six newly sequenced type strains into 19 phylogenomic groups—18 groups (A to R) in the Enterobacter cloacae complex and Enterobacter aerogenes. Diverse mechanisms underlying the molecular evolutionary trajectory of these drug-resistant Enterobacter spp. were revealed, including the acquisition of an antibiotic resistance plasmid, followed by clonal spread, horizontal transfer of blaKPC-harboring plasmids between different phylogenomic groups, and repeated transposition of the blaKPC gene among different plasmid backbones. Group A, which comprises multilocus sequence type 171 (ST171), was the most commonly identified (23% of isolates). Genomic analysis showed that ST171 isolates evolved from a common ancestor and formed two different major clusters; each acquiring unique blaKPC-harboring plasmids, followed by clonal expansion. The data presented here represent the first comprehensive study of phylogenomic interrogation and the relationship between antibiotic resistance and plasmid discrimination among carbapenem-resistant Enterobacter spp., demonstrating the genetic diversity and complexity of the molecular mechanisms driving antibiotic resistance in this genus. IMPORTANCE Enterobacter spp., especially carbapenemase-producing Enterobacter spp., have emerged as a clinically significant cause of nosocomial infections. However, only limited information is available on the distribution of carbapenem resistance across this genus. Augmenting this problem is an erroneous identification of Enterobacter strains because of ambiguous typing methods and imprecise taxonomy. In this study, we used a whole-genome-based comparative phylogenetic approach to (i) revisit and redefine the genus Enterobacter and (ii) unravel the emergence and evolution of the Klebsiella pneumoniae carbapenemase-harboring Enterobacter spp. Using genomic analysis of 447 sequenced strains, we developed an improved understanding of the species designations within this complex genus and identified the diverse mechanisms driving the molecular evolution of carbapenem resistance. The findings in this study provide a solid genomic framework that will serve as an important resource in the future development of molecular diagnostics and in supporting drug discovery programs.
format	article
author	Kalyan D. Chavda Liang Chen Derrick E. Fouts Granger Sutton Lauren Brinkac Stephen G. Jenkins Robert A. Bonomo Mark D. Adams Barry N. Kreiswirth
author_facet	Kalyan D. Chavda Liang Chen Derrick E. Fouts Granger Sutton Lauren Brinkac Stephen G. Jenkins Robert A. Bonomo Mark D. Adams Barry N. Kreiswirth
author_sort	Kalyan D. Chavda
title	Comprehensive Genome Analysis of Carbapenemase-Producing <italic toggle="yes">Enterobacter</italic> spp.: New Insights into Phylogeny, Population Structure, and Resistance Mechanisms
title_short	Comprehensive Genome Analysis of Carbapenemase-Producing <italic toggle="yes">Enterobacter</italic> spp.: New Insights into Phylogeny, Population Structure, and Resistance Mechanisms
title_full	Comprehensive Genome Analysis of Carbapenemase-Producing <italic toggle="yes">Enterobacter</italic> spp.: New Insights into Phylogeny, Population Structure, and Resistance Mechanisms
title_fullStr	Comprehensive Genome Analysis of Carbapenemase-Producing <italic toggle="yes">Enterobacter</italic> spp.: New Insights into Phylogeny, Population Structure, and Resistance Mechanisms
title_full_unstemmed	Comprehensive Genome Analysis of Carbapenemase-Producing <italic toggle="yes">Enterobacter</italic> spp.: New Insights into Phylogeny, Population Structure, and Resistance Mechanisms
title_sort	comprehensive genome analysis of carbapenemase-producing <italic toggle="yes">enterobacter</italic> spp.: new insights into phylogeny, population structure, and resistance mechanisms
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/5929499c28984899965978be8bf2cb94
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Comprehensive Genome Analysis of Carbapenemase-Producing <italic toggle="yes">Enterobacter</italic> spp.: New Insights into Phylogeny, Population Structure, and Resistance Mechanisms

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