title: Salmonella type III effector SpvC, a phosphothreonine lyase, contributes to reduction in inflammatory response during intestinal phase of infection.
abstract: Salmonella phosphothreonine lyase SpvC inactivates the dual-phosphorylated host mitogen-activated protein kinases (MAPK) through β-elimination. While SpvC can be secreted in vitro by both Salmonella pathogenicity island (SPI)-1 and SPI-2 type III secretion systems (T3SSs), translocation of this protein into the host cell cytosol has only been demonstrated by SPI-2 T3SS. In this study, we show that SpvC can be delivered into the host cell cytoplasm by both SPI-1 and SPI-2 T3SSs. Dephosphorylation of the extracellular signal-regulated protein kinases (ERK) was detected in an SPI-1 T3SS-dependent manner 2 h post infection. Using a mouse model for Salmonella enterocolitis, which was treated with streptomycin prior to infection, we observed that mice infected with Salmonella enterica serovar Typhimurium strains lacking the spvC gene showed pronounced colitis when compared with mice infected with the wild-type strain 1 day after infection. The effect of SpvC on the development of colitis was characterized by reduced mRNA levels of the pro-inflammatory cytokines and chemokines, and reduced inflammation with less infiltration of neutrophils. Furthermore, the reduction in inflammation by SpvC resulted in increased bacterial dissemination in spleen of mice infected with Salmonella. Collectively, our findings suggest that SpvC exerts as an anti-inflammatory effector and the attenuation of intestinal inflammatory response by SpvC is involved in systemic infection of Salmonella.
authors.affiliation: Department of Microbiology, School of Pharmacy, Kitasato University, Tokyo 108-8641, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Haneda
authors.forename: Yuta
authors.initials: Y
authors.lastname: Ishii
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Shimizu
authors.forename: Keiko
authors.initials: K
authors.lastname: Ohshima
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Iida
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Danbara
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okada
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism; D058947:Bacterial Secretion Systems; D019757:Carbon-Oxygen Lyases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D003600:Cytosol / Q000276:immunology; D004760:Enterocolitis / Q000276:immunology / Q000382:microbiology; D005260:Female; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000382:microbiology*; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012475:Salmonella / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D012480:Salmonella Infections / Q000276:immunology* / Q000382:microbiology; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D013307:Streptomycin / Q000008:administration & dosage
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D008565:Membrane Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; C440638:SPI-2 protein, Salmonella; C419942:Spi1 protein, Salmonella; D020928:Mitogen-Activated Protein Kinases; D019757:Carbon-Oxygen Lyases; C527194:phosphothreonine lyase, Salmonella enterica; D013307:Streptomycin