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Autophagy and endosomal trafficking inhibition by Vibrio cholerae MARTX toxin phosphatidylinositol-3-phosphate-specific phospholipase A1 activity

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posted on 29.08.2016 by S. Agarwal, H. Kim, R. B. Chan, R. Williamson, W. Cho, G. D. Paolo, K. J. F. Satchell
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.

Funding

This work was supported by an Investigators in the Pathogenesis of Infectious Disease award from the Burroughs Wellcome Fund and by NIH R01 grants AI051490, AI092825 and AI098369 (to KJFS), NS056049 (to GDP), and GM68849 (to WC).

History

Publisher Statement

This is a copy of an article published in the Nature Communications. © 2015 Macmillan Publishers Limited. All rights reserved. © The Author(s). www.nature.com/naturecommunications.

Publisher

Nature Publishing Group

Language

en_US

issn

2041-1723

Issue date

26/10/2015

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