TY - JOUR
T1 - PLEKHM1 regulates salmonella-containing vacuole biogenesis and infection
AU - McEwan, David G.
AU - Richter, Benjamin
AU - Claudi, Beatrice
AU - Wigge, Christoph
AU - Wild, Philipp
AU - Farhan, Hesso
AU - McGourty, Kieran
AU - Coxon, Fraser P.
AU - Franz-Wachtel, Mirita
AU - Perdu, Bram
AU - Akutsu, Masato
AU - Habermann, Anja
AU - Kirchof, Anja
AU - Helfrich, Miep H.
AU - Odgren, Paul R.
AU - Van Hul, Wim
AU - Frangakis, Achilleas S.
AU - Rajalingam, Krishnaraj
AU - Macek, Boris
AU - Holden, David W.
AU - Bumann, Dirk
AU - Dikic, Ivan
N1 - Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/1/14
Y1 - 2015/1/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84920984853&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2014.11.011
DO - 10.1016/j.chom.2014.11.011
M3 - Article
C2 - 25500191
AN - SCOPUS:84920984853
SN - 1931-3128
VL - 17
SP - 58
EP - 71
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 1
ER -