Role for the Burkholderia pseudomallei Type Three Secretion System Cluster 1 bpscN Gene in Virulence

Burkholderia pseudomallei , the causal agent of melioidosis, employs a number of virulence factors during its infection of mammalian cells. One such factor is the type three secretion system (TTSS), which is proposed to mediate the transport and secretion of bacterial effector molecules directly into host cells. TheB. pseudomallei genome contains three TTSS gene clusters (designated TTSS1, TTSS2, and TTSS3). Previous research has indicated that neither TTSS1 nor TTSS2 is involved inB. pseudomallei virulence in a hamster infection model. We have characterized aB. pseudomallei mutant lacking expression of the predicted TTSS1 ATPase encoded bybpscN . This mutant was significantly attenuated for virulence in a respiratory melioidosis mouse model of infection. In addition, analysesin vitro showed diminished survival and replication in RAW264.7 cells and an increased level of colocalization with the autophagy marker protein LC3 but an unhindered ability to escape from phagosomes. Taken together, these data provide evidence that the TTSS1bpscN gene product plays an important role in the intracellular survival ofB. pseudomallei and the pathogenesis of murine infection.