Genomic Characterization of Burkholderia pseudomallei Isolates Selected for Medical Countermeasures Testing

Comparative Genomics Associated with Differential Virulence

Jason Sahl, Christopher Allender, Rebecca Colman, Katy J Califf, James Schupp, Bart Currie, Kristopher Zandt, H. Carl Gelhaus, Paul Keim, Apichai Tuanyok

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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 LSBSR. 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.
Original languageEnglish
Article numbere0121052
Pages (from-to)1-18
Number of pages18
JournalPLoS One
Volume10
Issue number3
DOIs
Publication statusPublished - 2015

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Burkholderia pseudomallei
Genomics
Virulence
virulence
Genes
genomics
Testing
Genome
genome
Animals
Melioidosis
genes
Single Nucleotide Polymorphism
testing
animals
pathogenesis
single nucleotide polymorphism
Burkholderia Infections
Biological Warfare Agents
bioterrorism

Cite this

Sahl, Jason ; Allender, Christopher ; Colman, Rebecca ; Califf, Katy J ; Schupp, James ; Currie, Bart ; Zandt, Kristopher ; Gelhaus, H. Carl ; Keim, Paul ; Tuanyok, Apichai. / Genomic Characterization of Burkholderia pseudomallei Isolates Selected for Medical Countermeasures Testing : Comparative Genomics Associated with Differential Virulence. In: PLoS One. 2015 ; Vol. 10, No. 3. pp. 1-18.
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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 LSBSR. 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.",
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Genomic Characterization of Burkholderia pseudomallei Isolates Selected for Medical Countermeasures Testing : Comparative Genomics Associated with Differential Virulence. / Sahl, Jason; Allender, Christopher; Colman, Rebecca; Califf, Katy J; Schupp, James; Currie, Bart; Zandt, Kristopher; Gelhaus, H. Carl; Keim, Paul; Tuanyok, Apichai.

In: PLoS One, Vol. 10, No. 3, e0121052, 2015, p. 1-18.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Sahl, Jason

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AU - Califf, Katy J

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