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Title
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PLEKHM1 regulates salmonella-containing vacuole biogenesis and infection
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Author
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Abstract
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| 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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Language
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English
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Source (journal)
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Cell host & microbe. - Place of publication unknown
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Publication
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Place of publication unknown
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2015
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ISSN
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1931-3128
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DOI
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10.1016/J.CHOM.2014.11.011
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Volume/pages
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17
:1
(2015)
, p. 58-71
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ISI
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000348030100010
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Pubmed ID
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25500191
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Full text (Publisher's DOI)
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