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

Author:

Chimalapati Suneeta12,de Souza Santos Marcela1,Lafrance Alexander E1,Ray Ann3ORCID,Lee Wan-Ru4,Rivera-Cancel Giomar5ORCID,Vale Gonçalo6,Pawlowski Krzysztof17,Mitsche Matthew A68,McDonald Jeffrey G68,Liou Jen4ORCID,Orth Kim125ORCID

Affiliation:

1. Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, United States

2. Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States

3. Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, United States

4. Department of Physiology, University of Texas Southwestern Medical Center, Dallas, United States

5. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States

6. Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, United States

7. Faculty of Agriculture and Biology, Warsaw University of Life Sciences, Warsaw, Poland

8. Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, United States

Abstract

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.

Funder

National Institutes of Health

Once Upon A Time Foundation

Welch Foundation

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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