Mycobacterium tuberculosis ESX-1-secreted substrate protein EspC promotes mycobacterial survival through endoplasmic reticulum stress-mediated apoptosis.

ABSTRACT: EsxA, secreted by the ESAT-6 secretion system 1 (ESX-1) secretion system, is considered the major Mycobacterium tuberculosis (Mtb) virulence determinant. However, the roles of the individual ESX-1 substrates, such as EspC, remain unclear due to their interdependency for secretion with EsxA. Here, we validated that EspC triggered ER stress-mediated apoptosis in macrophages. The EspC-mediated ER stress was involved in pro-inflammatory cytokines generation, intracellular Ca₂₊ release, and reactive oxygen species accumulation. Mitochondrial transmembrane potential dissipation and mitochondrial outer membrane permeabilization occurred in EspC-treated macrophages, causing apoptosis. Furthermore, ER stress-mediated apoptosis was effectively induced in EspC-overexpressing

SUBMITTER: Guo Q 

PROVIDER: S-EPMC7832037 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature