RT Journal Article
SR Electronic
T1 Post-phagocytosis activation of NLRP3 inflammasome by two novel T6SS effectors
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.08.11.503615
DO 10.1101/2022.08.11.503615
A1 Hadar Cohen
A1 Noam Baram
A1 Chaya M. Fridman
A1 Liat Edry-Botzer
A1 Dor Salomon
A1 Motti Gerlic
YR 2022
UL http://biorxiv.org/content/early/2022/08/12/2022.08.11.503615.abstract
AB The type VI secretion system (T6SS) is used by bacteria to deliver toxic effectors directly into target cells. Most T6SSs mediate antibacterial activities, whereas the potential anti-eukaryotic role of T6SS remains understudied. Here, we found a Vibrio T6SS that delivers two novel effectors into mammalian host immune cells. We showed that these effectors induce a pyroptotic cell death in a phagocytosis-dependent manner; we identified the NLRP3 inflammasome as being the underlying mechanism leading to the T6SS-induced pyroptosis. Moreover, we identified a compensatory T6SS-induced pathway that is activated upon inhibition of the canonical pyroptosis pathway. Genetic analyses revealed possible horizontal spread of this T6SS and its anti-eukaryotic effectors into emerging pathogens in the marine environment. Our findings reveal novel T6SS effectors that activate the host inflammasome and possibly contribute to virulence and to the emergence of bacterial pathogens.