Portimine A toxin causes skin inflammation through ZAKα-dependent NLRP1 inflammasome activation.

In 2020-2021, a "mysterious illness" struck Senegalese fishermen, causing severe acute dermatitis in over one thousand individuals following exposure through drift-net fishing activity. Here, by performing deep analysis of the environmental samples we reveal the presence of the marine dinoflagellate Vulcanodinium rugosum and its associated cyclic imine toxins. Specifically, we show that the toxin PortimineA, strongly enriched in environmental samples, impedes ribosome function in human keratinocytes, which subsequently activates the stress kinases ZAKα and P38 and promotes the nucleation of the human NLRP1 inflammasome, leading to the release of IL-1β/IL-18 pro-inflammatory cytokines and cell death.

Uncovering a new family of conserved virulence factors that promote the production of host-damaging outer membrane vesicles in gram-negative bacteria.

CprA is a short-chain dehydrogenase/reductase (SDR) that contributes to resistance against colistin and antimicrobial peptides. The cprA gene is conserved across Pseudomonas aeruginosa clades and its expression is directly regulated by the two-component system PmrAB. We have shown that cprA expression leads to the production of outer membrane vesicles (OMVs) that block autophagic flux and have a greater capacity to activate the non-canonical inflammasome pathway.