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bioRxiv · 10.1101/2024.07.11.603062

T3SS translocon induces pyroptosis by direct interaction with NLRC4/NAIP inflammasome

Zhao, Y.·Zhu, H.·Li, J.·Sun, L.
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Abstract

Type III secretion system (T3SS) is a virulence apparatus existing in many bacterial pathogens. Structurally, T3SS consists of the base, needle, tip, and translocon. The NLRC4 inflammasome is the major receptor for T3SS needle and basal rod proteins. Whether other T3SS components are recognized by NLRC4 is unclear. In this study, using Edwardsiella tarda as a model intracellular pathogen, we examined T3SS-inflammasome interaction and its effect on cell death. E. tarda induced pyroptosis in a manner that required the bacterial translocon and the host inflammasome proteins of NLRC4, NLRP3, ASC, and caspase 1/4. The translocon protein EseB triggered NLRC4/NAIP-mediated pyroptosis by binding NAIP via its C-terminal region, particularly the terminal 6 residues (T6R). EseB homologs exist widely in T3SS-positive bacteria and share high identities in T6R. Like E. tarda EseB, all of the representatives of the EseB homologs exhibited T6R-dependent NLRC4 activation ability. Together these results revealed the function and molecular mechanism of EseB to induce host cell pyroptosis and suggested a highly conserved inflammasome-activation mechanism of T3SS translocon in bacterial pathogens.

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Zhao, Y., Zhu, H., Li, J., Sun, L.. 2024-07-16. T3SS translocon induces pyroptosis by direct interaction with NLRC4/NAIP inflammasome. https://doi.org/10.1101/2024.07.11.603062

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