Regulation of Type VI Secretion Systems of Burkholderia during transition to intracellular lifestyle

Pathogenic bacteria tightly regulate gene expression in response to environmental cues. In Burkholderia species, the Type VI Secretion Systems (T6SS) mediate interbacterial competition and host cell interactions. Here, we show that B. thailandensis switches from the anti-bacterial T6SS-1 to the anti-eukaryotic T6SS-5 during phagosomal maturation. While T6SS-1 expression persists in the host cells, its assembly progressively declines with increasing T6SS-5 expression. This switch is controlled by the two-component system VirAG as deletion of virA blocks T6SS-5 expression and restores T6SS-1 assembly in host cells. Furthermore, we found that deletion of T6SS-5 membrane complex restores T6SS-1 assembly in host cells. Notably, T6SS-1 activity in host cells induces mitochondrial fragmentation and apoptosis. Our data suggest that Burkholderia has evolved a mechanism to silence T6SS-1 upon host entry to preserve its replicative niche.