A Mutant ofBurkholderia pseudomallei, Auxotrophic in the Branched Chain Amino Acid Biosynthetic Pathway, Is Attenuated and Protective in a Murine Model of Melioidosis

Abstract

Using a transposon mutagenesis approach, we have identified a mutant ofBurkholderia pseudomalleithat is auxotrophic for branched chain amino acids. The transposon was shown to have interrupted theilvIgene encoding the large subunit of the acetolactate synthase enzyme. Compared to the wild type, this mutant was significantly attenuated in a murine model of disease. Mice inoculated intraperitoneally with the auxotrophic mutant, 35 days prior to challenge, were protected against a challenge dose of 6,000 median lethal doses of wild-typeB. pseudomallei.