Type VI Secretion System Accessory Protein TagAB-5 Promotes Pathogenicity in Human Microglia

Central nervous system (CNS) melioidosis caused by is being increasingly reported. Because of the high mortality associated with CNS melioidosis, understanding the underlying mechanism of pathogenesis in the CNS needs to be intensively investigated to develop better therapeutic strategies against this deadly disease. The type VI secretion system (T6SS) is a multiprotein machine that uses a spring-like mechanism to inject effectors into target cells to benefit the infection process. In this study, the role of the T6SS accessory protein TagAB-5 in pathogenicity was examined using the human microglial cell line HCM3, a unique resident immune cell of the CNS acting as a primary mediator of inflammation. We constructed mutant and complementary strains by the markerless allele replacement method. The effects of deletion on the pathogenicity of were studied by bacterial infection assays of HCM3 cells. Compared with the wild type, the mutant exhibited defective pathogenic abilities in intracellular replication, multinucleated giant cell formation, and induction of cell damage. Additionally, infection by the mutant elicited a decreased production of interleukin 8 (IL-8) in HCM3, suggesting that efficient pathogenicity of is required for IL-8 production in microglia. However, no significant differences in virulence in the model were observed between the mutant and the wild type. Taken together, this study indicated that microglia might be an important intracellular niche for particularly in CNS infection, and TagAB-5 confers pathogenicity in these cells.