Population Genomic Analysis of 1,777 Extended-Spectrum Beta-Lactamase-Producing Klebsiella pneumoniae Isolates, Houston, Texas: Unexpected Abundance of Clonal Group 307.

S Wesley Long,James J Davis,Thomas Brettin,Fangfang Xia,Stephen B Beres,Randall J Olsen,James M Musser,Todd N Eagar,Picheng Zhao,Steven J Projan

doi:10.1128/mbio.00489-17

S Wesley Long, James J Davis + Show 8 more

Open Access

https://doi.org/10.1128/mbio.00489-17

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Journal: mBio	Publication Date: May 16, 2017
Citations: 131	License type: CC BY 4.0

Affiliation: Houston Methodist, University of Chicago

Abstract

ABSTRACTKlebsiella 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.

Highlights

Klebsiella pneumoniae is a major human pathogen responsible for high morbidity and mortality rates
We identified no statistically significant difference between the observed in-hospital mortality rate of all patients infected with clonal group 307 (CG307) strains and that of patients infected with the Clonal group 258 (CG258) clonal type (Fig. 2)
CG307 strains caused more infections than the pandemic CG258 strains throughout the study period (Fig. 3)

Summary

Introduction

Klebsiella pneumoniae is a major human pathogen responsible for high morbidity and mortality rates. 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. Evidence suggests that there is circulation of K. pneumoniae clones within hospitals, with transmissible resistance plasmids shared between Klebsiella spp. and other pathogens [5, 17,18,19,20] This sharing of resistance elements is believed to have contributed to the emergence of multidrug resistance in K. pneumoniae and large, hospital-based outbreaks. The increasing reports of these nosocomial outbreaks are of great clinical concern [21, 22]

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