SdhA blocks disruption of the Legionella-containing vacuole by hijacking the OCRL phosphatase

Summary: Legionella pneumophila grows intracellularly within a replication vacuole via action of Icm/Dot-secreted proteins. One such protein, SdhA, maintains the integrity of the vacuolar membrane, thereby preventing cytoplasmic degradation of bacteria. We show here that SdhA binds and blocks the ac...

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Autores principales:	Won Young Choi, Seongok Kim, Philipp Aurass, Wenwen Huo, Elizabeth A. Creasey, Marc Edwards, Martin Lowe, Ralph R. Isberg
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Legionella pneumophila intracellular replication bacterial pathogenesis vesicle trafficking endosomes OCRL Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/68d2299132fb4f0b9cf551af7808893d
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spelling	oai:doaj.org-article:68d2299132fb4f0b9cf551af7808893d2021-11-04T04:28:53ZSdhA blocks disruption of the Legionella-containing vacuole by hijacking the OCRL phosphatase2211-124710.1016/j.celrep.2021.109894https://doaj.org/article/68d2299132fb4f0b9cf551af7808893d2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211124721013644https://doaj.org/toc/2211-1247Summary: Legionella pneumophila grows intracellularly within a replication vacuole via action of Icm/Dot-secreted proteins. One such protein, SdhA, maintains the integrity of the vacuolar membrane, thereby preventing cytoplasmic degradation of bacteria. We show here that SdhA binds and blocks the action of OCRL (OculoCerebroRenal syndrome of Lowe), an inositol 5-phosphatase pivotal for controlling endosomal dynamics. OCRL depletion results in enhanced vacuole integrity and intracellular growth of a sdhA mutant, consistent with OCRL participating in vacuole disruption. Overexpressed SdhA alters OCRL function, enlarging endosomes, driving endosomal accumulation of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2), and interfering with endosomal trafficking. SdhA interrupts Rab guanosine triphosphatase (GTPase)-OCRL interactions by binding to the OCRL ASPM-SPD2-Hydin (ASH) domain, without directly altering OCRL 5-phosphatase activity. The Legionella vacuole encompassing the sdhA mutant accumulates OCRL and endosomal antigen EEA1 (Early Endosome Antigen 1), consistent with SdhA blocking accumulation of OCRL-containing endosomal vesicles. Therefore, SdhA hijacking of OCRL is associated with blocking trafficking events that disrupt the pathogen vacuole.Won Young ChoiSeongok KimPhilipp AurassWenwen HuoElizabeth A. CreaseyMarc EdwardsMartin LoweRalph R. IsbergElsevierarticleLegionella pneumophilaintracellular replicationbacterial pathogenesisvesicle traffickingendosomesOCRLBiology (General)QH301-705.5ENCell Reports, Vol 37, Iss 5, Pp 109894- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Legionella pneumophila intracellular replication bacterial pathogenesis vesicle trafficking endosomes OCRL Biology (General) QH301-705.5
spellingShingle	Legionella pneumophila intracellular replication bacterial pathogenesis vesicle trafficking endosomes OCRL Biology (General) QH301-705.5 Won Young Choi Seongok Kim Philipp Aurass Wenwen Huo Elizabeth A. Creasey Marc Edwards Martin Lowe Ralph R. Isberg SdhA blocks disruption of the Legionella-containing vacuole by hijacking the OCRL phosphatase
description	Summary: Legionella pneumophila grows intracellularly within a replication vacuole via action of Icm/Dot-secreted proteins. One such protein, SdhA, maintains the integrity of the vacuolar membrane, thereby preventing cytoplasmic degradation of bacteria. We show here that SdhA binds and blocks the action of OCRL (OculoCerebroRenal syndrome of Lowe), an inositol 5-phosphatase pivotal for controlling endosomal dynamics. OCRL depletion results in enhanced vacuole integrity and intracellular growth of a sdhA mutant, consistent with OCRL participating in vacuole disruption. Overexpressed SdhA alters OCRL function, enlarging endosomes, driving endosomal accumulation of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2), and interfering with endosomal trafficking. SdhA interrupts Rab guanosine triphosphatase (GTPase)-OCRL interactions by binding to the OCRL ASPM-SPD2-Hydin (ASH) domain, without directly altering OCRL 5-phosphatase activity. The Legionella vacuole encompassing the sdhA mutant accumulates OCRL and endosomal antigen EEA1 (Early Endosome Antigen 1), consistent with SdhA blocking accumulation of OCRL-containing endosomal vesicles. Therefore, SdhA hijacking of OCRL is associated with blocking trafficking events that disrupt the pathogen vacuole.
format	article
author	Won Young Choi Seongok Kim Philipp Aurass Wenwen Huo Elizabeth A. Creasey Marc Edwards Martin Lowe Ralph R. Isberg
author_facet	Won Young Choi Seongok Kim Philipp Aurass Wenwen Huo Elizabeth A. Creasey Marc Edwards Martin Lowe Ralph R. Isberg
author_sort	Won Young Choi
title	SdhA blocks disruption of the Legionella-containing vacuole by hijacking the OCRL phosphatase
title_short	SdhA blocks disruption of the Legionella-containing vacuole by hijacking the OCRL phosphatase
title_full	SdhA blocks disruption of the Legionella-containing vacuole by hijacking the OCRL phosphatase
title_fullStr	SdhA blocks disruption of the Legionella-containing vacuole by hijacking the OCRL phosphatase
title_full_unstemmed	SdhA blocks disruption of the Legionella-containing vacuole by hijacking the OCRL phosphatase
title_sort	sdha blocks disruption of the legionella-containing vacuole by hijacking the ocrl phosphatase
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/68d2299132fb4f0b9cf551af7808893d
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SdhA blocks disruption of the Legionella-containing vacuole by hijacking the OCRL phosphatase

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