Vibrio deploys type 2 secreted lipase to esterify cholesterol with host fatty acids and mediate cell egress
Suneeta Chimalapati,
Marcela de Souza Santos,
Alexander E Lafrance,
Ann Ray,
Wan-Ru Lee,
Giomar Rivera-Cancel,
Gonçalo Vale,
Krzysztof Pawlowski,
Matthew A Mitsche,
Jeffrey G McDonald,
Jen Liou,
Kim Orth
Affiliations
Suneeta Chimalapati
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, United States; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States
Marcela de Souza Santos
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, United States
Alexander E Lafrance
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, United States
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States
Gonçalo Vale
Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, United States
Krzysztof Pawlowski
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, United States; Faculty of Agriculture and Biology, Warsaw University of Life Sciences, Warsaw, Poland
Matthew A Mitsche
Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, United States; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, United States
Jeffrey G McDonald
Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, United States; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, United States
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, United States; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States
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.
