Autophagy and endosomal trafficking inhibition by Vibrio cholerae MARTX toxin phosphatidylinositol-3-phosphate-specific phospholipase A1 activity.
Vibrio cholerae, responsible for acute gastroenteritis secretes a large multifunctional-autoprocessing repeat-in-toxin (MARTX) toxin linked to evasion of host immune system, facilitating colonization of small intestine. Unlike other effector domains of the multifunctional toxin that target cytoskeleton, the function of alpha-beta hydrolase (ABH) remained elusive. This study demonstrates that ABH is an esterase/lipase with catalytic Ser-His-Asp triad. ABH binds with high affinity to phosphatidylinositol-3-phosphate (PtdIns3P) and cleaves the fatty acid in PtdIns3P at the sn1 position in vitro making it the first PtdIns3P-specific phospholipase A1 (PLA1). Expression of ABH in vivo reduces intracellular PtdIns3P levels and its PtdIns3P-specific PLA1 activity blocks endosomal and autophagic pathways. In accordance with recent studies acknowledging the potential of extracellular pathogens to evade or exploit autophagy to prevent their clearance and facilitate survival, this is the first report highlighting the role of ABH in inhibiting autophagy and endosomal trafficking induced by extracellular V. cholerae.
Department of Microbiology-Immunology, Northwestern University, Feinberg School of Medicine, 303 E Chicago Avenue, Chicago, Illinois 60611, USA.
Shivani
S
Agarwal
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607, USA.
Hyunjin
H
Kim
Department of Pathology and Cell Biology, 630 West 168th Street, Columbia University, New York, New York 10032, USA.
Robin B
RB
Chan
Department of Microbiology-Immunology, Northwestern University, Feinberg School of Medicine, 303 E Chicago Avenue, Chicago, Illinois 60611, USA.
Shivangi
S
Agarwal
Department of Pathology and Cell Biology, 630 West 168th Street, Columbia University, New York, New York 10032, USA.
Rebecca
R
Williamson
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607, USA.
Wonhwa
W
Cho
Department of Pathology and Cell Biology, 630 West 168th Street, Columbia University, New York, New York 10032, USA.
Gilbert Di
GD
Paolo
Department of Pathology and Cell Biology, 630 West 168th Street, Columbia University, New York, New York 10032, USA.
Gilbert D
GD
Paolo
Department of Microbiology-Immunology, Northwestern University, Feinberg School of Medicine, 303 E Chicago Avenue, Chicago, Illinois 60611, USA.
Karla J F
KJ
Satchell
D001343:Autophagy / Q000187:drug effects; D001427:Bacterial Toxins / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D002771:Cholera / Q000378:metabolism / Q000382:microbiology / Q000503:physiopathology*; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D054466:Phospholipases A1 / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D014734:Vibrio cholerae / Q000201:enzymology* / Q000502:physiology
D001427:Bacterial Toxins; D018129:Phosphatidylinositol Phosphates; C434464:RtxA protein, Vibrio cholerae; C055525:phosphatidylinositol 3-phosphate; D054466:Phospholipases A1