TY - JOUR
T1 - Vibrio deploys type 2 secreted lipase to esterify cholesterol with host fatty acids and mediate cell egress
AU - Chimalapati, Suneeta
AU - Santos, Marcela de Souza
AU - Lafrance, Alexander E.
AU - Ray, Ann
AU - Lee, Wan Ru
AU - Rivera-Cancel, Giomar
AU - Vale, Gonçalo
AU - Pawlowski, Krzysztof
AU - Mitsche, Matthew A.
AU - McDonald, Jeffrey G.
AU - Liou, Jen
AU - Orth, Kim
N1 - Funding Information:
We thank members of the Orth lab for their discussions and editing. We thank Dr. Arun Radhakrishnan for valuable discussions and providing cholesterol/MCD reagents. This work was funded NIH grants R01 GM115188 and RO1 GM113079, Once Upon a Time. . .Foundation and the Welch Foundation I-1561. Dr. Jeffery G McDonald is supported by PO1 HL20948. Dr. Jen Liou is a Sowell Family Scholar in Medical Research. Dr. Kim Orth is a Burroughs Welcome Investigator, a Beckman Young Investigator, and a W W Caruth, Jr., Biomedical Scholar with an Earl A Forsythe Chair in Biomedical Science.
Funding Information:
We thank members of the Orth lab for their discussions and editing. We thank Dr. Arun Radhakrishnan for valuable discussions and providing cholesterol/MCD reagents. This work was funded NIH grants R01 GM115188 and RO1 GM113079, Once Upon a Time?Foundation and the Welch Foundation I-1561. Dr. Jeffery G McDonald is supported by PO1 HL20948. Dr. Jen Liou is a Sowell Family Scholar in Medical Research. Dr. Kim Orth is a Burroughs Welcome Investigator, a Beckman Young Investigator, and a W W Caruth, Jr., Biomedical Scholar with an Earl A Forsythe Chair in Biomedical Science.
Publisher Copyright:
© Chimalapati et al.
PY - 2020/8
Y1 - 2020/8
N2 - 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.
AB - 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.
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U2 - 10.7554/ELIFE.58057
DO - 10.7554/ELIFE.58057
M3 - Article
C2 - 32808593
AN - SCOPUS:85089630786
SN - 2050-084X
VL - 9
SP - 1
EP - 22
JO - eLife
JF - eLife
M1 - e58057
ER -