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Interrogation of the Burkholderia pseudomallei genome to address differential virulence among isolates.
PLoS One. 2014; 9(12):e115951.Plos

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 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.

Authors+Show Affiliations

Los Alamos National Laboratory, Bioscience Division, Los Alamos, NM, United States of America.Los Alamos National Laboratory, Bioscience Division, Los Alamos, NM, United States of America.US Army Medical Research Institute of Infectious Diseases, Bacteriology Division, Fort Detrick, MD, United States of America.US Army Medical Research Institute of Infectious Diseases, Bacteriology Division, Fort Detrick, MD, United States of America.US Army Medical Research Institute of Infectious Diseases, Biostatistics Division, Fort Detrick, MD, United States of America.US Army Medical Research Institute of Infectious Diseases, Bacteriology Division, Fort Detrick, MD, United States of America.US Army Medical Research Institute of Infectious Diseases, Bacteriology Division, Fort Detrick, MD, United States of America.US Army Medical Research Institute of Infectious Diseases, Bacteriology Division, Fort Detrick, MD, United States of America.Defense Threat Reduction Agency, Chemical and Biological Technologies Department, Fort Belvoir, VA, United States of America.

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

25536074

Citation

Challacombe, Jean F., et al. "Interrogation of the Burkholderia Pseudomallei Genome to Address Differential Virulence Among Isolates." PloS One, vol. 9, no. 12, 2014, pp. e115951.
Challacombe JF, Stubben CJ, Klimko CP, et al. Interrogation of the Burkholderia pseudomallei genome to address differential virulence among isolates. PLoS One. 2014;9(12):e115951.
Challacombe, J. F., Stubben, C. J., Klimko, C. P., Welkos, S. L., Kern, S. J., Bozue, J. A., Worsham, P. L., Cote, C. K., & Wolfe, D. N. (2014). Interrogation of the Burkholderia pseudomallei genome to address differential virulence among isolates. PloS One, 9(12), e115951. https://doi.org/10.1371/journal.pone.0115951
Challacombe JF, et al. Interrogation of the Burkholderia Pseudomallei Genome to Address Differential Virulence Among Isolates. PLoS One. 2014;9(12):e115951. PubMed PMID: 25536074.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interrogation of the Burkholderia pseudomallei genome to address differential virulence among isolates. AU - Challacombe,Jean F, AU - Stubben,Chris J, AU - Klimko,Christopher P, AU - Welkos,Susan L, AU - Kern,Steven J, AU - Bozue,Joel A, AU - Worsham,Patricia L, AU - Cote,Christopher K, AU - Wolfe,Daniel N, Y1 - 2014/12/23/ PY - 2014/06/17/received PY - 2014/12/01/accepted PY - 2014/12/24/entrez PY - 2014/12/24/pubmed PY - 2015/12/15/medline SP - e115951 EP - e115951 JF - PloS one JO - PLoS One VL - 9 IS - 12 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/25536074/Interrogation_of_the_Burkholderia_pseudomallei_genome_to_address_differential_virulence_among_isolates_ L2 - https://dx.plos.org/10.1371/journal.pone.0115951 DB - PRIME DP - Unbound Medicine ER -