PLEKHM1 regulates Salmonella-containing vacuole biogenesis and infection.
Cell Host Microbe
; 17(1): 58-71, 2015 Jan 14.
Article
em En
| MEDLINE
| ID: mdl-25500191
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Salmonella typhimurium
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Proteínas de Bactérias
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Vacúolos
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Glicoproteínas de Membrana
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Glicoproteínas
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Proteínas Adaptadoras de Transdução de Sinal
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Interações Hospedeiro-Patógeno
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article