title: Growth and killing of a Salmonella enterica serovar Typhimurium sifA mutant strain in the cytosol of different host cell lines.
abstract: Intracellular pathogens have developed different mechanisms which enable their survival and replication within the host cells. Some survive and replicate within a membrane-bound vacuole modified by the bacteria to support microbial growth (e.g. Salmonella enterica serovar Typhimurium), whereas others escape from the vacuole into the host cell cytosol, where they proliferate (e.g. Listeria monocytogenes). In this study a Salmonella strain carrying a mutation in sifA which is released from the vacuole was used to analyse Salmonella survival and replication within the cytosol of several cell lines. It was found that Salmonella replicates within the cytosol of epithelial cells at a higher rate than that achieved when replicating within the vacuole, but is defective for replication in the cytosol of fibroblasts or macrophages. Using an aroC purD double mutant strain which does not replicate within host cells, it was shown that Salmonella encounters a killing activity within the cytosol of macrophages. Furthermore, in vitro experiments using cytosol extracted from either infected or uninfected macrophages suggested that this activity is activated upon Salmonella infection.
authors.affiliation: Department of Infectious Diseases, Centre for Molecular Microbiology and Infection, Imperial College School of Medicine, Armstrong Road, London SW7 2AZ, UK1.
authors.forename: Carmen R
authors.initials: CR
authors.lastname: Beuzón
authors.affiliation: Department of Infectious Diseases, Centre for Molecular Microbiology and Infection, Imperial College School of Medicine, Armstrong Road, London SW7 2AZ, UK1.
authors.forename: Suzana P
authors.initials: SP
authors.lastname: Salcedo
authors.affiliation: Department of Infectious Diseases, Centre for Molecular Microbiology and Infection, Imperial College School of Medicine, Armstrong Road, London SW7 2AZ, UK1.
authors.forename: David W
authors.initials: DW
authors.lastname: Holden
mesh_terms: D001426:Bacterial Proteins; D002460:Cell Line; D003600:Cytosol / Q000382:microbiology; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000235:genetics*; D049452:Green Fluorescent Proteins; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000378:metabolism; D008264:Macrophages / Q000382:microbiology* / Q000502:physiology; D008854:Microscopy, Electron; D009154:Mutation; D012486:Salmonella typhimurium / Q000235:genetics / Q000254:growth & development* / Q000502:physiology; D014617:Vacuoles / Q000378:metabolism* / Q000382:microbiology
chemical_list: D001426:Bacterial Proteins; D006023:Glycoproteins; D008164:Luminescent Proteins; C421862:SifA protein, Salmonella; D049452:Green Fluorescent Proteins