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Genomic Characterization of Burkholderia pseudomallei Isolates Selected for Medical Countermeasures Testing: Comparative Genomics Associated with Differential Virulence

Sahl, Jason W., Allender, Christopher J., Colman, Rebecca E., Califf, Katy J., Schupp, James M., Currie, Bart J., Van Zandt, Kristopher E., Gelhaus, H. Carl, Keim, Paul and Tuanyok, Apichai (2015). Genomic Characterization of Burkholderia pseudomallei Isolates Selected for Medical Countermeasures Testing: Comparative Genomics Associated with Differential Virulence. PLoS One,10(3 - Article No. e0121052).

Document type: Journal Article
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IRMA ID 11381xPUB61
Title Genomic Characterization of Burkholderia pseudomallei Isolates Selected for Medical Countermeasures Testing: Comparative Genomics Associated with Differential Virulence
Author Sahl, Jason W.
Allender, Christopher J.
Colman, Rebecca E.
Califf, Katy J.
Schupp, James M.
Currie, Bart J.
Van Zandt, Kristopher E.
Gelhaus, H. Carl
Keim, Paul
Tuanyok, Apichai
Journal Name PLoS One
Publication Date 2015
Volume Number 10
Issue Number 3 - Article No. e0121052
ISSN 1932-6203   (check CDU catalogue  open catalogue search in new window)
Scopus ID 2-s2.0-84925865074
Total Pages 18
Place of Publication United States of America
Publisher Public Library of Science
HERDC Category C1 - Journal Article (DIISR)
Abstract Burkholderia pseudomallei is the causative agent of melioidosis and a potential bioterrorism agent. In the development of medical countermeasures against B. pseudomallei infection, the US Food and Drug Administration (FDA) animal Rule recommends using well-characterized strains in animal challenge studies. In this study, whole genome sequence data were generated for 6 B. pseudomallei isolates previously identified as candidates for animal challenge studies; an additional 5 isolates were sequenced that were associated with human inhalational melioidosis. A core genome single nucleotide polymorphism (SNP) phylogeny inferred from a concatenated SNP alignment from the 11 isolates sequenced in this study and a diverse global collection of isolates demonstrated the diversity of the proposed Animal Rule isolates. To understand the genomic composition of each isolate, a large-scale blast score ratio (LS-BSR) analysis was performed on the entire pan-genome; this demonstrated the variable composition of genes across the panel and also helped to identify genes unique to individual isolates. In addition, a set of ~550 genes associated with pathogenesis in B. pseudomallei were screened against the 11 sequenced genomes with LS-BSR. Differential gene distribution for 54 virulence-associated genes was observed between genomes and three of these genes were correlated with differential virulence observed in animal challenge studies using BALB/c mice. Differentially conserved genes and SNPs associated with disease severity were identified and could be the basis for future studies investigating the pathogenesis of B. pseudomallei. Overall, the genetic characterization of the 11 proposed Animal Rule isolates provides context for future studies involving B. pseudomallei pathogenesis, differential virulence, and efficacy to therapeutics.
DOI http://dx.doi.org/10.1371/journal.pone.0121052   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)
Additional Notes This is an Open Access article distributed under the terms of the Creative Commons Attribution License 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Description for Link Link to CC Attribution 4.0 License
URL https://creativecommons.org/licenses/by/4.0/au


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