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

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.

doi:10.1371/journal.pone.0115951

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

Journal Article · Tue Dec 23 00:00:00 EST 2014 · PLoS ONE

DOI:https://doi.org/10.1371/journal.pone.0115951· OSTI ID:1193442

Challacombe, Jean F. ^[1]; Stubben, Chris J. ^[1]; Klimko, Christopher P. ^[2]; Welkos, Susan L. ^[2]; Kern, Steven J. ^[2]; Bozue, Joel A. ^[2]; Worsham, Patricia L. ^[2]; Cote, Christopher K. ^[2]; Wolfe, Daniel N. ^[3]; Badger, Jonathan H.

Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD (United States)
Defense Threat Reduction Agency, Fort Belvoir, VA (United States)

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.

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Research Organization:: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC52-06NA25396

OSTI ID:: 1193442

Alternate ID(s):: OSTI ID: 1201465

Report Number(s):: LA-UR-14-28692

Journal Information:: PLoS ONE, Vol. 9, Issue 12; ISSN 1932-6203

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 15 works

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