Continuing Evolution of Burkholderia mallei Through Genome Reduction and Large-Scale Rearrangements

Abstract

Burkholderia mallei (Bm), the causative agent of the predominately equine disease glanders, is a genetically uniform species that is very closely related to the much more diverse species Burkholderia pseudomallei (Bp), an opportunistic human pathogen and the primary cause of melioidosis. To gain insight into the relative lack of genetic diversity within Bm, we performed whole-genome comparative analysis of seven Bm strains and contrasted these with eight Bp strains. The Bm core genome (shared by all seven strains) is smaller in size than that of Bp, but the inverse is true for the variable gene sets that are distributed across strains. Interestingly, the biological roles of the Bm variable gene sets are much more homogeneous than those of Bp. The Bm variable genes are found mostly in contiguous regions flanked by insertion sequence (IS) elements, which appear to mediate excision and subsequent elimination of groups of genes that are under reduced selection in the mammalian host. The analysis suggests that the Bm genome continues to evolve through random IS-mediated recombination events, and differences in gene content may contribute to differences in virulence observed among Bm strains. The results are consistent with the view that Bm recently evolved from a single strain of Bp upon introduction into an animal host followed by expansion of IS elements, prophage elimination, and genome rearrangements and reduction mediated by homologous recombination across IS elements.

Antibodies against In Vivo -Expressed Antigens Are Sufficient To Protect against Lethal Aerosol Infection with Burkholderia mallei and Burkholderia pseudomallei

“…The genetic relatedness between the organisms indicates that B. mallei evolved from B. pseudomallei through a process of genomic reduction (24)(25)(26)(27). The genes retained by B. mallei have an average identity of 99% at the nucleotide level with their B. pseudomallei orthologs, and of those, 650 have been proposed to form a core virulome based on comparative genomic analysis and sequence similarity to known virulence factors (28).…”

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

“…Although B. thailandensis is considered relatively nonpathogenic, it has occasionally been associated with human infection, and high inocula can cause disease in mice (6)(7)(8). B. mallei, an obligate pathogen of equine hosts that causes glanders, is a clonal descendant of B. pseudomallei that has undergone considerable genome decay, losing the capacity for survival in the environment (3,9).…”

Comparative Phylogenomics and Evolution of the Brucellae Reveal a Path to Virulence

“…The adaptation of certain Alphaproteobacteria to intracellular life within a host has been associated with genome reduction, resulting in the loss of genes no longer necessary in this specialized environment (1,2). Free-living bacteria in water or soil must exploit diverse conditions and compete with other organisms in these environments, while bacteria that reside within host cells encounter less competition but are exposed to different stresses (3,4). As facultative intracellular pathogens, Brucella species establish long-term, often chronic, interactions with higher eukaryotes (1) but also must survive outside the host.…”