Bacterial-induced cell fusion is a danger signal triggering cGAS-STING pathway via micronuclei formation.

ABSTRACT: Burkholderia pseudomallei is the causative agent of melioidosis, an infectious disease in the tropics and subtropics with high morbidity and mortality. The facultative intracellular bacterium induces host cell fusion through its type VI secretion system 5 (T6SS5) as an important part of its pathogenesis in mammalian hosts. This allows it to spread intercellularly without encountering extracellular host defenses. We report that bacterial T6SS5-dependent cell fusion triggers type I IFN gene expression in the host and leads to activation of the cGAMP synthase-stimulator of IFN genes (cGAS-STING) pathway, independent of bacterial ligands. Aberrant and abortive mitotic events result in the formation of micronuclei colocalizing with cGAS, which is activated by double-stranded DNA. Surpris

SUBMITTER: Ku JWK 

PROVIDER: S-EPMC7355030 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature