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Title: Interrogation of the Burkholderia pseudomallei genome to address differential virulence among isolates

Abstract

Infection by the Gram-negative pathogen Burkholderia pseudomallei results in the disease melioidosis, acquired from the environment in parts of southeast Asia and northern Australia. Clinical symptoms of melioidosis range from acute (fever, pneumonia, septicemia, and localized infection) to chronic (abscesses in various organs and tissues, most commonly occurring in the lungs, liver, spleen, kidney, prostate and skeletal muscle), and persistent infections in humans are difficult to cure. Understanding the basic biology and genomics of B. pseudomallei is imperative for the development of new vaccines and therapeutic interventions. This formidable task is becoming more tractable due to the increasing number of B. pseudomallei genomes that are being sequenced and compared. Here, we compared three B. pseudomallei genomes, from strains MSHR668, K96243 and 1106a, to identify features that might explain why MSHR668 is more virulent than K96243 and 1106a in a mouse model of B. pseudomallei infection. Our analyses focused on metabolic, virulence and regulatory genes that were present in MSHR668 but absent from both K96243 and 1106a. We also noted features present in K96243 and 1106a but absent from MSHR668, and identified genomic differences that may contribute to variations in virulence noted among the three B. pseudomallei isolates. While this workmore » contributes to our understanding of B. pseudomallei genomics, more detailed experiments are necessary to characterize the relevance of specific genomic features to B. pseudomallei metabolism and virulence. Functional analyses of metabolic networks, virulence and regulation shows promise for examining the effects of B. pseudomallei on host cell metabolism and will lay a foundation for future prediction of the virulence of emerging strains. Continued emphasis in this area will be critical for protection against melioidosis, as a better understanding of what constitutes a fully virulent Burkholderia isolate may provide for better diagnostic and medical countermeasure strategies.« less

Authors:
 [1];  [1];  [2];  [2];  [2];  [2];  [2];  [2];  [3];
  1. Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
  2. U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD (United States)
  3. Defense Threat Reduction Agency, Fort Belvoir, VA (United States)
Publication Date:
Research Org.:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1193442
Alternate Identifier(s):
OSTI ID: 1201465
Report Number(s):
LA-UR-14-28692
Journal ID: ISSN 1932-6203
Grant/Contract Number:  
AC52-06NA25396
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
PLoS ONE
Additional Journal Information:
Journal Volume: 9; Journal Issue: 12; Journal ID: ISSN 1932-6203
Publisher:
Public Library of Science
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Challacombe, Jean F., Stubben, Chris J., Klimko, Christopher P., Welkos, Susan L., Kern, Steven J., Bozue, Joel A., Worsham, Patricia L., Cote, Christopher K., Wolfe, Daniel N., and Badger, Jonathan H. Interrogation of the Burkholderia pseudomallei genome to address differential virulence among isolates. United States: N. p., 2014. Web. doi:10.1371/journal.pone.0115951.
Challacombe, Jean F., Stubben, Chris J., Klimko, Christopher P., Welkos, Susan L., Kern, Steven J., Bozue, Joel A., Worsham, Patricia L., Cote, Christopher K., Wolfe, Daniel N., & Badger, Jonathan H. Interrogation of the Burkholderia pseudomallei genome to address differential virulence among isolates. United States. doi:10.1371/journal.pone.0115951.
Challacombe, Jean F., Stubben, Chris J., Klimko, Christopher P., Welkos, Susan L., Kern, Steven J., Bozue, Joel A., Worsham, Patricia L., Cote, Christopher K., Wolfe, Daniel N., and Badger, Jonathan H. Tue . "Interrogation of the Burkholderia pseudomallei genome to address differential virulence among isolates". United States. doi:10.1371/journal.pone.0115951. https://www.osti.gov/servlets/purl/1193442.
@article{osti_1193442,
title = {Interrogation of the Burkholderia pseudomallei genome to address differential virulence among isolates},
author = {Challacombe, Jean F. and Stubben, Chris J. and Klimko, Christopher P. and Welkos, Susan L. and Kern, Steven J. and Bozue, Joel A. and Worsham, Patricia L. and Cote, Christopher K. and Wolfe, Daniel N. and Badger, Jonathan H.},
abstractNote = {Infection by the Gram-negative pathogen Burkholderia pseudomallei results in the disease melioidosis, acquired from the environment in parts of southeast Asia and northern Australia. Clinical symptoms of melioidosis range from acute (fever, pneumonia, septicemia, and localized infection) to chronic (abscesses in various organs and tissues, most commonly occurring in the lungs, liver, spleen, kidney, prostate and skeletal muscle), and persistent infections in humans are difficult to cure. Understanding the basic biology and genomics of B. pseudomallei is imperative for the development of new vaccines and therapeutic interventions. This formidable task is becoming more tractable due to the increasing number of B. pseudomallei genomes that are being sequenced and compared. Here, we compared three B. pseudomallei genomes, from strains MSHR668, K96243 and 1106a, to identify features that might explain why MSHR668 is more virulent than K96243 and 1106a in a mouse model of B. pseudomallei infection. Our analyses focused on metabolic, virulence and regulatory genes that were present in MSHR668 but absent from both K96243 and 1106a. We also noted features present in K96243 and 1106a but absent from MSHR668, and identified genomic differences that may contribute to variations in virulence noted among the three B. pseudomallei isolates. While this work contributes to our understanding of B. pseudomallei genomics, more detailed experiments are necessary to characterize the relevance of specific genomic features to B. pseudomallei metabolism and virulence. Functional analyses of metabolic networks, virulence and regulation shows promise for examining the effects of B. pseudomallei on host cell metabolism and will lay a foundation for future prediction of the virulence of emerging strains. Continued emphasis in this area will be critical for protection against melioidosis, as a better understanding of what constitutes a fully virulent Burkholderia isolate may provide for better diagnostic and medical countermeasure strategies.},
doi = {10.1371/journal.pone.0115951},
journal = {PLoS ONE},
issn = {1932-6203},
number = 12,
volume = 9,
place = {United States},
year = {2014},
month = {12}
}

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