PLEKHM1 regulates Salmonella-containing vacuole biogenesis and infection.

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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Autophagy-Related Proteins, Bacterial Proteins, Carrier Proteins, Glycoproteins, Host-Pathogen Interactions, Humans, Intracellular Signaling Peptides and Proteins, Membrane Glycoproteins, Membrane Proteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Nuclear Proteins, Protein Binding, Protein Interaction Mapping, Salmonella typhimurium, Vacuoles, rab GTP-Binding Proteins, rab7 GTP-Binding Proteins
Cell Host Microbe
Date: Jan. 14, 2015
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