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

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...

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Main Authors: Jean F Challacombe, Chris J Stubben, Christopher P Klimko, Susan L Welkos, Steven J Kern, Joel A Bozue, Patricia L Worsham, Christopher K Cote, Daniel N Wolfe
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0115951
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author Jean F Challacombe
Chris J Stubben
Christopher P Klimko
Susan L Welkos
Steven J Kern
Joel A Bozue
Patricia L Worsham
Christopher K Cote
Daniel N Wolfe
author_facet Jean F Challacombe
Chris J Stubben
Christopher P Klimko
Susan L Welkos
Steven J Kern
Joel A Bozue
Patricia L Worsham
Christopher K Cote
Daniel N Wolfe
author_sort Jean F Challacombe
collection DOAJ
description 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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spelling doaj.art-a3e7452a78694ee6aaa649f1031dbc382022-12-21T23:10:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01912e11595110.1371/journal.pone.0115951Interrogation of the Burkholderia pseudomallei genome to address differential virulence among isolates.Jean F ChallacombeChris J StubbenChristopher P KlimkoSusan L WelkosSteven J KernJoel A BozuePatricia L WorshamChristopher K CoteDaniel N WolfeInfection 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.https://doi.org/10.1371/journal.pone.0115951
spellingShingle Jean F Challacombe
Chris J Stubben
Christopher P Klimko
Susan L Welkos
Steven J Kern
Joel A Bozue
Patricia L Worsham
Christopher K Cote
Daniel N Wolfe
Interrogation of the Burkholderia pseudomallei genome to address differential virulence among isolates.
PLoS ONE
title Interrogation of the Burkholderia pseudomallei genome to address differential virulence among isolates.
title_full Interrogation of the Burkholderia pseudomallei genome to address differential virulence among isolates.
title_fullStr Interrogation of the Burkholderia pseudomallei genome to address differential virulence among isolates.
title_full_unstemmed Interrogation of the Burkholderia pseudomallei genome to address differential virulence among isolates.
title_short Interrogation of the Burkholderia pseudomallei genome to address differential virulence among isolates.
title_sort interrogation of the burkholderia pseudomallei genome to address differential virulence among isolates
url https://doi.org/10.1371/journal.pone.0115951
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