PLEKHM1 regulates Salmonella-containing vacuole biogenesis and infection
Department of Cell and Developmental Biology
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.
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Citation: Cell Host Microbe. 2015 Jan 14;17(1):58-71. doi: 10.1016/j.chom.2014.11.011. Link to article on publisher's site.
Cell host and microbe
McEwan, David G.; Odgren, Paul R.; Bumann, Dirk; and Dikic, Ivan, "PLEKHM1 regulates Salmonella-containing vacuole biogenesis and infection" (2015). Cell and Developmental Biology Publications and Presentations. Paper 141.