title: The Type III Secretion System Effector SeoC of Salmonella enterica subsp. salamae and S. enterica subsp. arizonae ADP-Ribosylates Src and Inhibits Opsonophagocytosis.
abstract: Salmonella species utilize type III secretion systems (T3SSs) to translocate effectors into the cytosol of mammalian host cells, subverting cell signaling and facilitating the onset of gastroenteritis. In this study, we compared a draft genome assembly of Salmonella enterica subsp. salamae strain 3588/07 against the genomes of S. enterica subsp. enterica serovar Typhimurium strain LT2 and Salmonella bongori strain 12419. S. enterica subsp. salamae encodes the Salmonella pathogenicity island 1 (SPI-1), SPI-2, and the locus of enterocyte effacement (LEE) T3SSs. Though several key S Typhimurium effector genes are missing (e.g., avrA, sopB, and sseL), S. enterica subsp. salamae invades HeLa cells and contains homologues of S. bongori sboK and sboC, which we named seoC SboC and SeoC are homologues of EspJ from enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively), which inhibit Src kinase-dependent phagocytosis by ADP-ribosylation. By screening 73 clinical and environmental Salmonella isolates, we identified EspJ homologues in S. bongori, S. enterica subsp. salamae, and Salmonella enterica subsp. arizonae The β-lactamase TEM-1 reporter system showed that SeoC is translocated by the SPI-1 T3SS. All the Salmonella SeoC/SboC homologues ADP-ribosylate Src E310 in vitro Ectopic expression of SeoC/SboC inhibited phagocytosis of IgG-opsonized beads into Cos-7 cells stably expressing green fluorescent protein (GFP)-FcγRIIa. Concurrently, S. enterica subsp. salamae infection of J774.A1 macrophages inhibited phagocytosis of beads, in a seoC-dependent manner. These results show that S. bongori, S. enterica subsp. salamae, and S. enterica subsp. arizonae share features of the infection strategy of extracellular pathogens EPEC and EHEC and shed light on the complexities of the T3SS effector repertoires of Enterobacteriaceae.
authors.affiliation: MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College, London, United Kingdom.
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Pollard
authors.affiliation: MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College, London, United Kingdom.
authors.forename: Joanna C
authors.initials: JC
authors.lastname: Young
authors.affiliation: MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College, London, United Kingdom.
authors.forename: Valentina
authors.initials: V
authors.lastname: Covarelli
authors.affiliation: Sección de Enterobacterias, Servicio de Bacteriología, Centro Nacional de Microbiología, ISCIII, Majadahonda, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Herrera-León
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Connor
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
authors.forename: Maria
authors.initials: M
authors.lastname: Fookes
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
authors.forename: Danielle
authors.initials: D
authors.lastname: Walker
authors.affiliation: Sección de Enterobacterias, Servicio de Bacteriología, Centro Nacional de Microbiología, ISCIII, Majadahonda, Spain.
authors.forename: Aurora
authors.initials: A
authors.lastname: Echeita
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.|The London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Thomson
authors.affiliation: MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College, London, United Kingdom.
authors.forename: Cedric N
authors.initials: CN
authors.lastname: Berger
authors.affiliation: MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College, London, United Kingdom g.frankel@imperial.ac.uk.
authors.forename: Gad
authors.initials: G
authors.lastname: Frankel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D016680:Genome, Bacterial; D006367:HeLa Cells; D006801:Humans; D015995:Prevalence; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism; D019779:Salmonella enterica / Q000145:classification* / Q000378:metabolism; D000069296:Type III Secretion Systems / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; C445323:FCGR2A protein, human; D017452:Receptors, IgG; D000069296:Type III Secretion Systems