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.

The Type VI Secretion System Spike Protein VgrG5 Mediates Membrane Fusion during Intercellular Spread by Pseudomallei Group Burkholderia Species

“…In Southeast Asia and Australia, where the endemicity of the organism is high, infections are nearly always acquired from the environment (1). Adaptations to avoid predation in the rhizosphere are thought to promote accidental virulence in mammals (2)(3)(4). The geographic distribution of B. pseudomallei overlaps with that of the closely related species B. thailandensis (5).…”

Dissection of the Burkholderia intracellular life cycle using a photothermal nanoblade

“…Infections acquired from the environment can lead to melioidosis, a serious and sometimes fatal human disease. Accumulating evidence suggests that adaptations selected in the rhizosphere are responsible for "accidental virulence" in mammals (3). Bp has a large (7.2 Mb) genome that has been shaped by extensive horizontal exchange (4).…”

Evolutionary Analysis of Burkholderia pseudomallei Identifies Putative Novel Virulence Genes, Including a Microbial Regulator of Host Cell Autophagy

“…We previously reported a comparative genomic analysis of 11 B. pseudomallei genomes, identifying 211 genes exhibiting signatures of positive selection (15). These positively selected genes were widely dispersed across diverse functions, including metabolic processes, membrane functions, signal transduction, and gene expression regulation.…”

“…In DNA sequence data, genes exhibiting positive selection can be broadly identified by comparing the rates of nonsynonymous to synonymous polymorphisms. We hypothesized that these positively selected genes, while overtly responding to environmental pressures encountered by B. pseudomallei in soil, might indirectly facilitate the colonization of mammalian hosts (15). Preliminary analysis supported the notion that some of these positively selected genes might interact with host cellular pathways.…”

“…If a gene model incorporating positive selection had a higher likelihood score than that of a null model without positive selection, this was regarded as evidence for positive selection. Using this approach, 211 genes were commonly identified by both models as being positively selected (15). For this study, we chose 26 positively selected genes among the originally identified 211 genes, using criteria described in Results and Discussion (Table 1).…”