title: A genomic survey of positive selection in Burkholderia pseudomallei provides insights into the evolution of accidental virulence.
abstract: Certain environmental microorganisms can cause severe human infections, even in the absence of an obvious requirement for transition through an animal host for replication ("accidental virulence"). To understand this process, we compared eleven isolate genomes of Burkholderia pseudomallei (Bp), a tropical soil microbe and causative agent of the human and animal disease melioidosis. We found evidence for the existence of several new genes in the Bp reference genome, identifying 282 novel genes supported by at least two independent lines of supporting evidence (mRNA transcripts, database homologs, and presence of ribosomal binding sites) and 81 novel genes supported by all three lines. Within the Bp core genome, 211 genes exhibited significant levels of positive selection (4.5%), distributed across many cellular pathways including carbohydrate and secondary metabolism. Functional experiments revealed that certain positively selected genes might enhance mammalian virulence by interacting with host cellular pathways or utilizing host nutrients. Evolutionary modifications improving Bp environmental fitness may thus have indirectly facilitated the ability of Bp to colonize and survive in mammalian hosts. These findings improve our understanding of the pathogenesis of melioidosis, and establish Bp as a model system for studying the genetics of accidental virulence.
authors.affiliation: Genome Institute of Singapore, Singapore, Republic of Singapore.
authors.forename: Tannistha
authors.initials: T
authors.lastname: Nandi
authors.forename: Catherine
authors.initials: C
authors.lastname: Ong
authors.forename: Arvind Pratap
authors.initials: AP
authors.lastname: Singh
authors.forename: Justin
authors.initials: J
authors.lastname: Boddey
authors.forename: Timothy
authors.initials: T
authors.lastname: Atkins
authors.forename: Mitali
authors.initials: M
authors.lastname: Sarkar-Tyson
authors.forename: Angela E
authors.initials: AE
authors.lastname: Essex-Lopresti
authors.forename: Hui Hoon
authors.initials: HH
authors.lastname: Chua
authors.forename: Talima
authors.initials: T
authors.lastname: Pearson
authors.forename: Jason F
authors.initials: JF
authors.lastname: Kreisberg
authors.forename: Christina
authors.initials: C
authors.lastname: Nilsson
authors.forename: Pramila
authors.initials: P
authors.lastname: Ariyaratne
authors.forename: Catherine
authors.initials: C
authors.lastname: Ronning
authors.forename: Liliana
authors.initials: L
authors.lastname: Losada
authors.forename: Yijun
authors.initials: Y
authors.lastname: Ruan
authors.forename: Wing-Kin
authors.initials: WK
authors.lastname: Sung
authors.forename: Donald
authors.initials: D
authors.lastname: Woods
authors.forename: Richard W
authors.initials: RW
authors.lastname: Titball
authors.forename: Ifor
authors.initials: I
authors.lastname: Beacham
authors.forename: Ian
authors.initials: I
authors.lastname: Peak
authors.forename: Paul
authors.initials: P
authors.lastname: Keim
authors.forename: William C
authors.initials: WC
authors.lastname: Nierman
authors.forename: Patrick
authors.initials: P
authors.lastname: Tan
mesh_terms: D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D016957:Burkholderia pseudomallei / Q000235:genetics* / Q000472:pathogenicity*; D005260:Female; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D005798:Genes, Bacterial; D016680:Genome, Bacterial; D008554:Melioidosis / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D014774:Virulence / Q000235:genetics