Vibrio deploys Type 2 secreted lipase to esterify cholesterol with host fatty acids and mediate cell egress

Marcela de Souza Santos, Suneeta Chimalapati, Ann Ray, Wan Ru Lee, Giomar Rivera-Cancel, Alexander Lafrance, Gonçalo Vale, Krzysztof Pawłowski, Matt Mitsche, Jeffrey G. McDonald, Jen Liou, Kim Orth

Research output: Contribution to journalArticlepeer-review

Abstract

Pathogens find diverse niches for survival inside host cells where replication occurs in a relatively protected environment. Vibrio parahaemolyticus, a facultative intracellular pathogen, uses its type 3 secretion system 2 (T3SS2) to invade and replicate inside host cells. However, after extensive analysis, the T3SS2 pathogenicity island appeared to lack a mechanism for egress of this bacterium from the invaded host cell. Using a combination of cell biology, microbial genetics and lipid biochemistry, we found that VPA0226, a constitutively secreted lipase, is required for escape of Vibrio parahaemolyticus from host cells. Remarkably, this lipase must be delivered into the host cytoplasm where it preferentially uses fatty acids associated with innate immune response (i.e. arachidonic acid, 20:4) to esterify cholesterol, weakening the plasma membrane and allowing egress of the bacteria. This study reveals the resourcefulness of microbes and the interplay between virulence systems to evolve an ingenious scheme for survival and escape.

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - Nov 12 2019

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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