Vibrio pore-forming leukocidin activates pyroptotic cell death via the NLRP3 inflammasome

Hadar Cohen, Noam Baram, Liat Edry-Botzer, Ariel Munitz, Dor Salomon*, Mordechay Gerlic

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Cell death mechanisms are central to combat infections and to drive inflammation. The inflammasome controls infection through activation of caspase-1 leading to either IL-1β dependent inflammation, or pyroptotic cell death in infected cells. Hemolysins, which are pore-forming toxins (PFTs), alter the permeability of the host target membrane, often leading to cell death. We previously discovered a leukocidin domain-containing PFT produced by the Gram-negative bacterium Vibrio proteolyticus, named VPRH. VPRH constitutes a distinct, understudied class within the leukocidin superfamily, which is distributed among several photogenic Vibrios. Since PFTs of other pathogens were shown to activate the inflammasome pathway, we hypothesized that VPRH-induced cell death is mediated by direct activation of the inflammasome in mammalian immune host cells. Indeed, we found that VPRH induced a two-step cell death in macrophages. The first, a rapid step, was mediated by activating the NLRP3 inflammasome, leading to caspase-1 activation that resulted in IL-1β secretion and pyroptosis. The second step was independent of the inflammasome; however, its mechanism remains unknown. This study sets the foundation for better understanding the immunological consequences of inflammasome activation by a new leukocidin class of toxins, which may be shared between marine bacteria and give rise to new pathogenic isolates.

Original languageEnglish
Pages (from-to)278-290
Number of pages13
JournalEmerging Microbes and Infections
Issue number1
StatePublished - 1 Jan 2020


  • Cell death
  • IL-1β
  • Vibrio
  • hemolysin
  • inflammasome
  • leukocidin
  • pore-forming
  • pyroptosis


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