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2021-11-02Zeitschriftenartikel
SdhA blocks disruption of the Legionella-containing vacuole by hijacking the OCRL phosphatase
dc.contributor.authorChoi, Won Young
dc.contributor.authorKim, Seongok
dc.contributor.authorAurass, Philipp
dc.contributor.authorHuo, Wenwen
dc.contributor.authorCreasey, Elizabeth A.
dc.contributor.authorEdwards, Marc
dc.contributor.authorLowe, Martin
dc.contributor.authorIsberg, Ralph R.
dc.date.accessioned2022-03-14T07:47:41Z
dc.date.available2022-03-14T07:47:41Z
dc.date.issued2021-11-02none
dc.identifier.other10.1016/j.celrep.2021.109894
dc.identifier.urihttp://edoc.rki.de/176904/9493
dc.description.abstractLegionella 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.eng
dc.language.isoengnone
dc.publisherRobert Koch-Institut
dc.rights(CC BY 3.0 DE) Namensnennung 3.0 Deutschlandger
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/de/
dc.subjectLegionella pneumophilaeng
dc.subjectintracellular replicationeng
dc.subjectbacterial pathogenesiseng
dc.subjectvesicle traffickingeng
dc.subjectendosomeseng
dc.subjectOCRLeng
dc.subject.ddc610 Medizin und Gesundheitnone
dc.titleSdhA blocks disruption of the Legionella-containing vacuole by hijacking the OCRL phosphatasenone
dc.typearticle
dc.identifier.urnurn:nbn:de:0257-176904/9493-6
dc.type.versionpublishedVersionnone
local.edoc.container-titleCell Reportsnone
local.edoc.container-issn2211-1247none
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttps://www.sciencedirect.com/science/article/pii/S2211124721013644?via%3Dihubnone
local.edoc.container-publisher-nameCell Pressnone
local.edoc.container-volume37none
local.edoc.container-issue5none
local.edoc.container-year2021none
dc.description.versionPeer Reviewednone

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