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

Author

Listed:
  • Shivani Agarwal

    (Northwestern University, Feinberg School of Medicine)

  • Hyunjin Kim

    (University of Illinois at Chicago)

  • Robin B. Chan

    (630 West 168th Street, Columbia University)

  • Shivangi Agarwal

    (Northwestern University, Feinberg School of Medicine)

  • Rebecca Williamson

    (630 West 168th Street, Columbia University)

  • Wonhwa Cho

    (University of Illinois at Chicago)

  • Gilbert Di Paolo

    (630 West 168th Street, Columbia University)

  • Karla J. F. Satchell

    (Northwestern University, Feinberg School of Medicine)

Abstract

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.

Suggested Citation

  • Shivani Agarwal & Hyunjin Kim & Robin B. Chan & Shivangi Agarwal & Rebecca Williamson & Wonhwa Cho & Gilbert Di Paolo & Karla J. F. Satchell, 2015. "Autophagy and endosomal trafficking inhibition by Vibrio cholerae MARTX toxin phosphatidylinositol-3-phosphate-specific phospholipase A1 activity," Nature Communications, Nature, vol. 6(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9745
    DOI: 10.1038/ncomms9745
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    Cited by:

    1. Aftab Nadeem & Athar Alam & Eric Toh & Si Lhyam Myint & Zia ur Rehman & Tao Liu & Marta Bally & Anna Arnqvist & Hui Wang & Jun Zhu & Karina Persson & Bernt Eric Uhlin & Sun Nyunt Wai, 2021. "Phosphatidic acid-mediated binding and mammalian cell internalization of the Vibrio cholerae cytotoxin MakA," PLOS Pathogens, Public Library of Science, vol. 17(3), pages 1-34, March.

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