Characterization of an isogenic bimA mutant in the ATS2021 strain of Burkholderia pseudomallei.

Encephalomyelitis is uncommon but is associated with Burkholderia pseudomallei strains whose bimA gene, encoding an actin-based motility protein, resembles bimA from Burkholderia mallei (designated bimABm). We previously characterized the virulence of B. pseudomallei wild-type ATS2021 (bimABm). In a mouse model of ATS2021 aerosol exposure, lesions and inflammatory cytokines in the brain were seen early post-exposure and reached the central nervous system (CNS) through the olfactory nerve. In the current study, the bimA allele in the wild-type ATS2021 was replaced with the bimABp, and virulence was assessed by estimations of LD50, histopathological analyses, and bacterial dissemination. ATS2021 bimABp reached the CNS but was significantly attenuated, with higher LD50 estimates, altered bacterial dissemination, and reduced neuroinflammation. The immune response in lungs, spleens, and brains from mice exposed to aerosols indicated either strain induced shared and divergent immune patterns. Finally, the evaluation of the host response in brains via NanoString transcriptomic platform analyses suggested that the wild-type ATS2021 induced substantial changes in astrocyte and microglial activation, oligodendrocyte function, and overall inflammatory signaling, compared to the mutant bimABp bacteria. These results support a direct role of the bimABm gene product for bacterial dissemination after inhalation.