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

Pathogens find diverse niches for survival including inside a host cell where replication occurs in a relatively protective environment. Vibrio parahaemolyticus is a facultative intracellular pathogen that uses its type 3 secretion system 2 (T3SS2) to invade and replicate inside host cells. Analysis of the T3SS2 pathogenicity island encoding the T3SS2 appeared to lack a mechanism for egress of this bacterium from the invaded host cell. Using a combination of molecular tools, we found that VPA0226, a constitutively secreted lipase, is required for escape of V. parahaemolyticus from the host cells. This lipase must be delivered into the host cytoplasm where it preferentially uses fatty acids associated with innate immune response 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 and host cell resources to evolve an ingenious scheme for survival and escape.

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

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.Impact StatementConsidering the course of a pathogen’s evolution, there appears to be interplay between secretion systems, providing unique, synergistic mechanisms to support a successful lifestyle for possibly pathogenesis, symbiosis and/or parasitosis.