Peer-Reviewed Journal Details
Mandatory Fields
McEwan DG;Richter B;Claudi B;Wigge C;Wild P;Farhan H;McGourty K;Coxon FP;Franz-Wachtel M;Perdu B;Akutsu M;Habermann A;Kirchof A;Helfrich MH;Odgren PR;Van Hul W;Frangakis AS;Rajalingam K;Macek B;Holden DW;Bumann D;Dikic I;
Cell Host & Microbe
PLEKHM1 regulates Salmonella-containing vacuole biogenesis and infection.
Optional Fields
The host endolysosomal compartment is often manipulated by intracellular bacterial pathogens. Salmonella (Salmonella enterica serovar Typhimurium) secrete numerous effector proteins, including SifA, through a specialized type III secretion system to hijack the host endosomal system and generate the Salmonella-containing vacuole (SCV). To form this replicative niche, Salmonella targets the Rab7 GTPase to recruit host membranes through largely unknown mechanisms. We show that Pleckstrin homology domain-containing protein family member 1 (PLEKHM1), a lysosomal adaptor, is targeted by Salmonella through direct interaction with SifA. By binding the PLEKHM1 PH2 domain, Salmonella utilize a complex containing PLEKHM1, Rab7, and the HOPS tethering complex to mobilize phagolysosomal membranes to the SCV. Depletion of PLEKHM1 causes a profound defect in SCV morphology with multiple bacteria accumulating in enlarged structures and significantly dampens Salmonella proliferation in multiple cell types and mice. Thus, PLEKHM1 provides a critical interface between pathogenic infection and the host endolysosomal system.
Grant Details