Brucella Rough Mutant Induce Macrophage Death via Activating IRE1α Pathway of Endoplasmic Reticulum Stress by Enhanced T4SS Secretion

摘要: Brucella is a Gram-negative facultative intracellular pathogen that causes the worldwide zoonosis, known as brucellosis. virulence relies mostly on its ability to invade and replicate within phagocytic cells. The type IV secretion system (T4SS) lipopolysaccharide are two major factors. rough mutants reportedly induce death of infected macrophages, which T4SS dependent. However, underlying molecular mechanism remains unclear. In this study, capacities mutant smooth wild-type strain were comparatively investigated, by constructing firefly luciferase fused effector, BPE123 VceC. addition, quantitative real-time PCR western blotting used analyze expression. results showed expression enhanced significantly in mutant. We also found activity virB operon promoter was notably increased mutant, depends quorum sensing-related regulators VjbR upregulation. Cell infection cell assays revealed deletion vjbR absolutely abolished cytotoxicity macrophages downregulating This suggests up-regulation promoted ΔrfbE contribute macrophage death. we via activating IRE1α pathway endoplasmic reticulum stress. Taken together, our study provide evidence comparison strain, upregulation increases transcription operon, resulting overexpression gene, accompanied over-secretion effecter proteins, thereby causing stress, suggesting novel insights into mechanisms associated with mutant-induced cytotoxicity.