The Burkholderia pseudomallei {Delta}asd mutant exhibits attenuated intracellular infectivity and imparts protection against acute inhalation melioidosis in mice.

Norris MH, Propst KL, Kang Y, Dow SW, Schweizer HP, Hoang TT.

Citation

Norris MH, Propst KL, Kang Y, Dow SW, Schweizer HP, Hoang TT. (2011) The Burkholderia pseudomallei {Delta}asd mutant exhibits attenuated intracellular infectivity and imparts protection against acute inhalation melioidosis in mice. Infection and Immunity 79(10):4010-4018.

Abstract

Burkholderia pseudomallei, the cause of serious and life threatening diseases in humans, is of national biodefense concern because of its potential use as a bioterrorism agent. This microbe is listed as a select agent by the CDC, therefore, development of vaccines is of significant importance. Here, we further investigated the growth characteristics of a recently created B. pseudomallei 1026b {Delta}asd mutant in vitro, in a cell model, and in an animal model of infection. The mutant was typified by an inability to grow in the absence of exogenous diaminopimelate (DAP) and, upon single-copy complementation with a wildtype copy of the asd gene, growth was restored to wildtype levels. Further characterization of the B. pseudomallei {Delta}asd mutant revealed a marked decrease in RAW264.7 murine macrophage cytotoxicity when compared to the wild-type and the complemented {Delta}asd mutant. RAW264.7 cells infected by the {Delta}asd mutant did not exhibit signs of cytopathology or multi-nucleated giant cell (MNGC) formation observed in wildtype B. pseudomallei cell infections. The {Delta}asd mutant was found to be avirulent in BALB/c mice and mice vaccinated with the mutant were protected against acute inhalation melioidosis. Thus, the B. pseudomallei {Delta}asd mutant may be a promising live-attenuated vaccine strain and a biosafe strain to be considered for exclusion from the select agent list.