Disruption of the Salmonella-containing vacuole leads to increased replication of Salmonella enterica serovar typhimurium in the cytosol of epithelial cells.
Salmonella enterica serovar Typhimurium is a facultative intracellular pathogen that inhabits a vacuolar compartment, called the Salmonella-containing vacuole (SCV), in infected host cells. Maintenance of the SCV is accomplished by SifA, and mutants of this Salmonella pathogenicity island 2 type III effector replicate more efficiently in epithelial cells. Here we demonstrate that enhanced replication of sifA mutants occurs in the cytosol of these cells. Increased replication of wild-type bacteria was also observed in cells treated with wortmannin or expressing Rab5 Q79L or Rab7 N125I, all of which caused a loss of SCV integrity. Our findings demonstrate the requirement of the host cell endosomal system for maintenance of the SCV and that loss of this compartment allows increased replication of serovar Typhimurium in the cytosol of epithelial cells.
Brumell
John H
JH
Biotechnology Laboratory and Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
Tang
Patrick
P
Zaharik
Michelle L
ML
Finlay
B Brett
BB
D015703:Antigens, CD / Q000378:metabolism; D001426:Bacterial Proteins; D003600:Cytosol / Q000382:microbiology; D011992:Endosomes / Q000382:microbiology; D004847:Epithelial Cells / Q000382:microbiology; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000378:metabolism / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000378:metabolism; D012486:Salmonella typhimurium / Q000254:growth & development*; D014617:Vacuoles / Q000378:metabolism / Q000382:microbiology; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
D015703:Antigens, CD; D001426:Bacterial Proteins; D006023:Glycoproteins; D008070:Lipopolysaccharides; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; C421862:SifA protein, Salmonella; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins