Population Genomic Analysis of 1,777 Extended-Spectrum Beta-Lactamase-Producing <italic toggle="yes">Klebsiella pneumoniae</italic> Isolates, Houston, Texas: Unexpected Abundance of Clonal Group 307

ABSTRACT Klebsiella pneumoniae is a major human pathogen responsible for high morbidity and mortality rates. The emergence and spread of strains resistant to multiple antimicrobial agents and documented large nosocomial outbreaks are especially concerning. To develop new therapeutic strategies for K...

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Autores principales:	S. Wesley Long, Randall J. Olsen, Todd N. Eagar, Stephen B. Beres, Picheng Zhao, James J. Davis, Thomas Brettin, Fangfang Xia, James M. Musser
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/aefb02ae61184449a27092f660cbfa6b
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spelling	oai:doaj.org-article:aefb02ae61184449a27092f660cbfa6b2021-11-15T15:51:29ZPopulation Genomic Analysis of 1,777 Extended-Spectrum Beta-Lactamase-Producing <italic toggle="yes">Klebsiella pneumoniae</italic> Isolates, Houston, Texas: Unexpected Abundance of Clonal Group 30710.1128/mBio.00489-172150-7511https://doaj.org/article/aefb02ae61184449a27092f660cbfa6b2017-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00489-17https://doaj.org/toc/2150-7511ABSTRACT Klebsiella pneumoniae is a major human pathogen responsible for high morbidity and mortality rates. The emergence and spread of strains resistant to multiple antimicrobial agents and documented large nosocomial outbreaks are especially concerning. To develop new therapeutic strategies for K. pneumoniae, it is imperative to understand the population genomic structure of strains causing human infections. To address this knowledge gap, we sequenced the genomes of 1,777 extended-spectrum beta-lactamase-producing K. pneumoniae strains cultured from patients in the 2,000-bed Houston Methodist Hospital system between September 2011 and May 2015, representing a comprehensive, population-based strain sample. Strains of largely uncharacterized clonal group 307 (CG307) caused more infections than those of well-studied epidemic CG258. Strains varied markedly in gene content and had an extensive array of small and very large plasmids, often containing antimicrobial resistance genes. Some patients with multiple strains cultured over time were infected with genetically distinct clones. We identified 15 strains expressing the New Delhi metallo-beta-lactamase 1 (NDM-1) enzyme that confers broad resistance to nearly all beta-lactam antibiotics. Transcriptome sequencing analysis of 10 phylogenetically diverse strains showed that the global transcriptome of each strain was unique and highly variable. Experimental mouse infection provided new information about immunological parameters of host-pathogen interaction. We exploited the large data set to develop whole-genome sequence-based classifiers that accurately predict clinical antimicrobial resistance for 12 of the 16 antibiotics tested. We conclude that analysis of large, comprehensive, population-based strain samples can assist understanding of the molecular diversity of these organisms and contribute to enhanced translational research. IMPORTANCE Klebsiella pneumoniae causes human infections that are increasingly difficult to treat because many strains are resistant to multiple antibiotics. Clonal group 258 (CG258) organisms have caused outbreaks in health care settings worldwide. Using a comprehensive population-based sample of extended-spectrum beta-lactamase (ESBL)-producing K. pneumoniae strains, we show that a relatively uncommon clonal type, CG307, caused the plurality of ESBL-producing K. pneumoniae infections in our patients. We discovered that CG307 strains have been abundant in Houston for many years. As assessed by experimental mouse infection, CG307 strains were as virulent as pandemic CG258 strains. Our results may portend the emergence of an especially successful clonal group of antibiotic-resistant K. pneumoniae.S. Wesley LongRandall J. OlsenTodd N. EagarStephen B. BeresPicheng ZhaoJames J. DavisThomas BrettinFangfang XiaJames M. MusserAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 8, Iss 3 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 S. Wesley Long Randall J. Olsen Todd N. Eagar Stephen B. Beres Picheng Zhao James J. Davis Thomas Brettin Fangfang Xia James M. Musser Population Genomic Analysis of 1,777 Extended-Spectrum Beta-Lactamase-Producing <italic toggle="yes">Klebsiella pneumoniae</italic> Isolates, Houston, Texas: Unexpected Abundance of Clonal Group 307
description	ABSTRACT Klebsiella pneumoniae is a major human pathogen responsible for high morbidity and mortality rates. The emergence and spread of strains resistant to multiple antimicrobial agents and documented large nosocomial outbreaks are especially concerning. To develop new therapeutic strategies for K. pneumoniae, it is imperative to understand the population genomic structure of strains causing human infections. To address this knowledge gap, we sequenced the genomes of 1,777 extended-spectrum beta-lactamase-producing K. pneumoniae strains cultured from patients in the 2,000-bed Houston Methodist Hospital system between September 2011 and May 2015, representing a comprehensive, population-based strain sample. Strains of largely uncharacterized clonal group 307 (CG307) caused more infections than those of well-studied epidemic CG258. Strains varied markedly in gene content and had an extensive array of small and very large plasmids, often containing antimicrobial resistance genes. Some patients with multiple strains cultured over time were infected with genetically distinct clones. We identified 15 strains expressing the New Delhi metallo-beta-lactamase 1 (NDM-1) enzyme that confers broad resistance to nearly all beta-lactam antibiotics. Transcriptome sequencing analysis of 10 phylogenetically diverse strains showed that the global transcriptome of each strain was unique and highly variable. Experimental mouse infection provided new information about immunological parameters of host-pathogen interaction. We exploited the large data set to develop whole-genome sequence-based classifiers that accurately predict clinical antimicrobial resistance for 12 of the 16 antibiotics tested. We conclude that analysis of large, comprehensive, population-based strain samples can assist understanding of the molecular diversity of these organisms and contribute to enhanced translational research. IMPORTANCE Klebsiella pneumoniae causes human infections that are increasingly difficult to treat because many strains are resistant to multiple antibiotics. Clonal group 258 (CG258) organisms have caused outbreaks in health care settings worldwide. Using a comprehensive population-based sample of extended-spectrum beta-lactamase (ESBL)-producing K. pneumoniae strains, we show that a relatively uncommon clonal type, CG307, caused the plurality of ESBL-producing K. pneumoniae infections in our patients. We discovered that CG307 strains have been abundant in Houston for many years. As assessed by experimental mouse infection, CG307 strains were as virulent as pandemic CG258 strains. Our results may portend the emergence of an especially successful clonal group of antibiotic-resistant K. pneumoniae.
format	article
author	S. Wesley Long Randall J. Olsen Todd N. Eagar Stephen B. Beres Picheng Zhao James J. Davis Thomas Brettin Fangfang Xia James M. Musser
author_facet	S. Wesley Long Randall J. Olsen Todd N. Eagar Stephen B. Beres Picheng Zhao James J. Davis Thomas Brettin Fangfang Xia James M. Musser
author_sort	S. Wesley Long
title	Population Genomic Analysis of 1,777 Extended-Spectrum Beta-Lactamase-Producing <italic toggle="yes">Klebsiella pneumoniae</italic> Isolates, Houston, Texas: Unexpected Abundance of Clonal Group 307
title_short	Population Genomic Analysis of 1,777 Extended-Spectrum Beta-Lactamase-Producing <italic toggle="yes">Klebsiella pneumoniae</italic> Isolates, Houston, Texas: Unexpected Abundance of Clonal Group 307
title_full	Population Genomic Analysis of 1,777 Extended-Spectrum Beta-Lactamase-Producing <italic toggle="yes">Klebsiella pneumoniae</italic> Isolates, Houston, Texas: Unexpected Abundance of Clonal Group 307
title_fullStr	Population Genomic Analysis of 1,777 Extended-Spectrum Beta-Lactamase-Producing <italic toggle="yes">Klebsiella pneumoniae</italic> Isolates, Houston, Texas: Unexpected Abundance of Clonal Group 307
title_full_unstemmed	Population Genomic Analysis of 1,777 Extended-Spectrum Beta-Lactamase-Producing <italic toggle="yes">Klebsiella pneumoniae</italic> Isolates, Houston, Texas: Unexpected Abundance of Clonal Group 307
title_sort	population genomic analysis of 1,777 extended-spectrum beta-lactamase-producing <italic toggle="yes">klebsiella pneumoniae</italic> isolates, houston, texas: unexpected abundance of clonal group 307
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/aefb02ae61184449a27092f660cbfa6b
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Population Genomic Analysis of 1,777 Extended-Spectrum Beta-Lactamase-Producing <italic toggle="yes">Klebsiella pneumoniae</italic> Isolates, Houston, Texas: Unexpected Abundance of Clonal Group 307

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