Population Genomic Analysis of 1,777 Extended-Spectrum Beta-Lactamase-Producing Klebsiella pneumoniae 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. 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 exploitedmore »
- Authors:
-
- Houston Methodist Research Inst. and Houston Methodist Hospital, Houston, TX (United States). Dept. of Pathology and Genomic Medicine. Center for Molecular and Translational Human Infectious Diseases Research; Cornell Univ., Ithaca, NY (United States). Weill Medical College. Dept. of Pathology and Lab. Medicine
- Houston Methodist Research Inst. and Houston Methodist Hospital, Houston, TX (United States). Dept. of Pathology and Genomic Medicine. Center for Molecular and Translational Human Infectious Diseases Research
- Argonne National Lab. (ANL), Argonne, IL (United States). Computing, Environment and Life Sciences; Univ. of Chicago, IL (United States). Computational Inst.
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC)
- OSTI Identifier:
- 1626108
- Grant/Contract Number:
- AC02-06CH11357
- Resource Type:
- Accepted Manuscript
- Journal Name:
- mBio (Online)
- Additional Journal Information:
- Journal Name: mBio (Online); Journal Volume: 8; Journal Issue: 3; Journal ID: ISSN 2150-7511
- Publisher:
- American Society for Microbiology (ASM)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Microbiology; Genome; Bacterial; Klebsiella Infections; Klebsiella pneumoniae; beta-lactamases
Citation Formats
Long, S. Wesley, Olsen, Randall J., Eagar, Todd N., Beres, Stephen B., Zhao, Picheng, Davis, James J., Brettin, Thomas, Xia, Fangfang, and Musser, James M. Population Genomic Analysis of 1,777 Extended-Spectrum Beta-Lactamase-Producing Klebsiella pneumoniae Isolates, Houston, Texas: Unexpected Abundance of Clonal Group 307. United States: N. p., 2017.
Web. doi:10.1128/mbio.00489-17.
Long, S. Wesley, Olsen, Randall J., Eagar, Todd N., Beres, Stephen B., Zhao, Picheng, Davis, James J., Brettin, Thomas, Xia, Fangfang, & Musser, James M. Population Genomic Analysis of 1,777 Extended-Spectrum Beta-Lactamase-Producing Klebsiella pneumoniae Isolates, Houston, Texas: Unexpected Abundance of Clonal Group 307. United States. https://doi.org/10.1128/mbio.00489-17
Long, S. Wesley, Olsen, Randall J., Eagar, Todd N., Beres, Stephen B., Zhao, Picheng, Davis, James J., Brettin, Thomas, Xia, Fangfang, and Musser, James M. Tue .
"Population Genomic Analysis of 1,777 Extended-Spectrum Beta-Lactamase-Producing Klebsiella pneumoniae Isolates, Houston, Texas: Unexpected Abundance of Clonal Group 307". United States. https://doi.org/10.1128/mbio.00489-17. https://www.osti.gov/servlets/purl/1626108.
@article{osti_1626108,
title = {Population Genomic Analysis of 1,777 Extended-Spectrum Beta-Lactamase-Producing Klebsiella pneumoniae Isolates, Houston, Texas: Unexpected Abundance of Clonal Group 307},
author = {Long, S. Wesley and Olsen, Randall J. and Eagar, Todd N. and Beres, Stephen B. and Zhao, Picheng and Davis, James J. and Brettin, Thomas and Xia, Fangfang and Musser, James M.},
abstractNote = {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.},
doi = {10.1128/mbio.00489-17},
journal = {mBio (Online)},
number = 3,
volume = 8,
place = {United States},
year = {Tue May 16 00:00:00 EDT 2017},
month = {Tue May 16 00:00:00 EDT 2017}
}
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- Antonopoulos, Dionysios A.; Assaf, Rida; Aziz, Ramy Karam
- Briefings in Bioinformatics, Vol. 20, Issue 4
Caribbean multi-centre study of Klebsiella pneumoniae: whole-genome sequencing, antimicrobial resistance and virulence factors
journal, May 2019
- Heinz, Eva; Brindle, Richard; Morgan-McCalla, Andrina
- Microbial Genomics, Vol. 5, Issue 5
High-resolution sweep metagenomics using fast probabilistic inference
journal, January 2020
- Mäklin, Tommi; Kallonen, Teemu; David, Sophia
- Wellcome Open Research, Vol. 5
High-resolution sweep metagenomics using fast probabilistic inference
journal, January 2020
- Mäklin, Tommi; Kallonen, Teemu; David, Sophia
- Wellcome Open Research, Vol. 5
Colonization, Infection, and the Accessory Genome of Klebsiella pneumoniae
journal, January 2018
- Martin, Rebekah M.; Bachman, Michael A.
- Frontiers in Cellular and Infection Microbiology, Vol. 8
A core genome approach that enables prospective and dynamic monitoring of infectious outbreaks
journal, May 2019
- Aggelen, Helen van; Kolde, Raivo; Chamarthi, Hareesh
- Scientific Reports, Vol. 9, Issue 1
No association between resistance mutations, empiric antibiotic, and mortality in ceftriaxone-resistant Escherichia coli and Klebsiella pneumoniae bacteremia
journal, August 2018
- Heng, Shi Thong; Chen, Swaine L.; Wong, Joshua G. X.
- Scientific Reports, Vol. 8, Issue 1