A Dual-Targeting T6SS DNase Drives Bacterial Antagonism and Eukaryotic Apoptosis via the cGAS-STING-TNF Axis.

ABSTRACT: The Type VI secretion system (T6SS) is a key virulence mechanism utilized by many Gram-negative bacteria to mediate the microbial competition and host pathogenesis. Despite the identification of diverse T6SS effectors targeting eukaryotic or prokaryotic cells, the trans-kingdom T6SS effectors that simultaneously target both eukaryotic and prokaryotic cells remain rarely reported. In this study, it is demonstrated that Yersinia pseudotuberculosis (Yptb) T6SS secretes a DNase effector, TkeA, which induces apoptosis in host cells. The translocation of TkeA into host cells causes nuclear DNA damage. This, in turn, activates the DNA-sensing cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway. The activation of the cGAS-STING pathway by TkeA subsequently triggers apopto

SUBMITTER: Song L 

PROVIDER: S-EPMC12302616 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature