Document Detail


Comparative genomics of Klebsiella pneumoniae strains with different antibiotic resistance profiles.
MedLine Citation:
PMID:  21746949     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
There is a global emergence of multidrug-resistant (MDR) strains of Klebsiella pneumoniae, a Gram-negative enteric bacterium that causes nosocomial and urinary tract infections. While the epidemiology of K. pneumoniae strains and occurrences of specific antibiotic resistance genes, such as plasmid-borne extended-spectrum β-lactamases (ESBLs), have been extensively studied, only four complete genomes of K. pneumoniae are available. To better understand the multidrug resistance factors in K. pneumoniae, we determined by pyrosequencing the nearly complete genome DNA sequences of two strains with disparate antibiotic resistance profiles, broadly drug-susceptible strain JH1 and strain 1162281, which is resistant to multiple clinically used antibiotics, including extended-spectrum β-lactams, fluoroquinolones, aminoglycosides, trimethoprim, and sulfamethoxazoles. Comparative genomic analysis of JH1, 1162281, and other published K. pneumoniae genomes revealed a core set of 3,631 conserved orthologous proteins, which were used for reconstruction of whole-genome phylogenetic trees. The close evolutionary relationship between JH1 and 1162281 relative to other K. pneumoniae strains suggests that a large component of the genetic and phenotypic diversity of clinical isolates is due to horizontal gene transfer. Using curated lists of over 400 antibiotic resistance genes, we identified all of the elements that differentiated the antibiotic profile of MDR strain 1162281 from that of susceptible strain JH1, such as the presence of additional efflux pumps, ESBLs, and multiple mechanisms of fluoroquinolone resistance. Our study adds new and significant DNA sequence data on K. pneumoniae strains and demonstrates the value of whole-genome sequencing in characterizing multidrug resistance in clinical isolates.
Authors:
Vinod Kumar; Peng Sun; Jessica Vamathevan; Yong Li; Karen Ingraham; Leslie Palmer; Jianzhong Huang; James R Brown
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2011-07-11
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  55     ISSN:  1098-6596     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-08-18     Completed Date:  2012-01-09     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4267-76     Citation Subset:  IM    
Affiliation:
Computational Biology, Quantitative Sciences, GlaxoSmithKline, King of Prussia, Pennsylvania, USA.
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MeSH Terms
Descriptor/Qualifier:
Aminoglycosides / pharmacology
Drug Resistance, Multiple, Bacterial / genetics
Fluoroquinolones / pharmacology
Genome, Bacterial / genetics*
Genomics / methods*
Klebsiella pneumoniae / drug effects,  genetics*
Sulfamethoxazole / pharmacology
Trimethoprim / pharmacology
beta-Lactams / pharmacology
Grant Support
ID/Acronym/Agency:
//Wellcome Trust
Chemical
Reg. No./Substance:
0/Aminoglycosides; 0/Fluoroquinolones; 0/beta-Lactams; 723-46-6/Sulfamethoxazole; 738-70-5/Trimethoprim
Comments/Corrections

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