Vibrio cholerae cytotoxin MakA induces noncanonical autophagy resulting in the spatial inhibition of canonical autophagyVisa övriga samt affilieringar
2021 (Engelska)Ingår i: Journal of Cell Science, ISSN 0021-9533, E-ISSN 1477-9137, Vol. 134, nr 5, artikel-id jcs252015Artikel i tidskrift (Refereegranskat) Published
Abstract [en]
Autophagy plays an essential role in the defense against manymicrobial pathogens as a regulator of both innate and adaptive immunity. Some pathogens have evolved sophisticated mechanisms that promote their ability to evade or subvert host autophagy. Here, we describe a novel mechanism of autophagy modulation mediated by the recently discovered Vibrio cholerae cytotoxin, motility-associatedkilling factor A (MakA). pH-dependent endocytosis of MakA by host cells resulted in the formation of a cholesterol-rich endolysosomal membrane aggregate in the perinuclear region. Aggregate formation induced the noncanonical autophagy pathway driving unconventional LC3 (herein referring to MAP1LC3B) lipidation on endolysosomal membranes. Subsequent sequestration of the ATG12-ATG5-ATG16L1 E3-like enzyme complex, required for LC3 lipidation at the membranous aggregate, resulted in an inhibition of both canonical autophagy and autophagy-related processes, including the unconventional secretion of interleukin-1β (IL-1β). These findings identify a novel mechanismof host autophagy modulation and immune modulation employed by V. cholerae during bacterial infection.
Ort, förlag, år, upplaga, sidor
The Company of Biologists , 2021. Vol. 134, nr 5, artikel-id jcs252015
Nyckelord [en]
IL-1β, MakA, Bacterial toxin, Membrane aggregate, Noncanonical autophagy, Unconventional secretion
Nationell ämneskategori
Cell- och molekylärbiologi Mikrobiologi inom det medicinska området
Identifikatorer
URN: urn:nbn:se:umu:diva-180836DOI: 10.1242/jcs.252015ISI: 000629619100016PubMedID: 33106317Scopus ID: 2-s2.0-85102218537OAI: oai:DiVA.org:umu-180836DiVA, id: diva2:1531261
Forskningsfinansiär
Knut och Alice Wallenbergs Stiftelse, KAW2015.0225Kempestiftelserna, JCK-15282021-02-252021-02-252024-07-02Bibliografiskt granskad