TY - JOUR T1 - SdhA blocks disruption of the Legionella-containing vacuole by hijacking the OCRL phosphatase AU - Choi, Won Young AU - Kim, Seongok AU - Aurass, Philipp AU - Huo, Wenwen AU - Creasey, Elizabeth A. AU - Edwards, Marc AU - Lowe, Martin AU - Isberg, Ralph R. AB - 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. KW - Legionella pneumophila KW - intracellular replication KW - bacterial pathogenesis KW - vesicle trafficking KW - endosomes KW - OCRL KW - 610 Medizin und Gesundheit PY - 2021 LA - eng PB - Robert Koch-Institut JO - Cell Reports VL - 37 IS - 5 DO - 10.1016/j.celrep.2021.109894 ER -