title: pH sensing by intracellular Salmonella induces effector translocation.
abstract: Salmonella enterica is an important intracellular bacterial pathogen of humans and animals. It replicates within host-cell vacuoles by delivering virulence (effector) proteins through a vacuolar membrane pore made by the Salmonella pathogenicity island 2 (SPI-2) type III secretion system (T3SS). T3SS assembly follows vacuole acidification, but when bacteria are grown at low pH, effector secretion is negligible. We found that effector secretion was activated at low pH from mutant strains lacking a complex of SPI-2-encoded proteins SsaM, SpiC, and SsaL. Exposure of wild-type bacteria to pH 7.2 after growth at pH 5.0 caused dissociation and degradation of SsaM/SpiC/SsaL complexes and effector secretion. In infected cells, loss of the pH 7.2 signal through acidification of host-cell cytosol prevented complex degradation and effector translocation. Thus, intravacuolar Salmonella senses host cytosolic pH, resulting in the degradation of regulatory complex proteins and effector translocation.
authors.affiliation: Section of Microbiology, Centre for Molecular Microbiology and Infection, Imperial College London, Armstrong Road, London SW7 2AZ, UK.
authors.forename: Xiu-Jun
authors.initials: XJ
authors.lastname: Yu
authors.forename: Kieran
authors.initials: K
authors.lastname: McGourty
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.forename: Kate E
authors.initials: KE
authors.lastname: Unsworth
authors.forename: David W
authors.initials: DW
authors.lastname: Holden
mesh_terms: D018407:Bacterial Physiological Phenomena; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003600:Cytosol / Q000737:chemistry; D044404:Genomic Islands; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018832:Molecular Chaperones / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism; D009154:Mutation; D012486:Salmonella typhimurium / Q000235:genetics / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity; D014617:Vacuoles / Q000378:metabolism / Q000382:microbiology*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D018832:Molecular Chaperones; D046912:Multiprotein Complexes; C120280:SpiC protein, Salmonella; C495986:SsaL protein, Salmonella typhimurium; C474475:SseB protein, Salmonella typhimurium; D037521:Virulence Factors
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