title: A Family of Salmonella Type III Secretion Effector Proteins Selectively Targets the NF-κB Signaling Pathway to Preserve Host Homeostasis.
abstract: Microbial infections usually lead to host innate immune responses and inflammation. These responses most often limit pathogen replication although they can also result in host-tissue damage. The enteropathogenic bacteria Salmonella Typhimurium utilizes a type III secretion system to induce intestinal inflammation by delivering specific effector proteins that stimulate signal transduction pathways resulting in the production of pro-inflammatory cytokines. We show here that a family of related Salmonella Typhimurium effector proteins PipA, GogA and GtgA redundantly target components of the NF-κB signaling pathway to inhibit transcriptional responses leading to inflammation. We show that these effector proteins are proteases that cleave both the RelA (p65) and RelB transcription factors but do not target p100 (NF-κB2) or p105 (NF-κB1). A Salmonella Typhimurium strain lacking these effectors showed increased ability to stimulate NF-κB and increased virulence in an animal model of infection. These results indicate that bacterial pathogens can evolve determinants to preserve host homeostasis and that those determinants can reduce the pathogen's virulence.
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Jana
authors.initials: J
authors.lastname: Kamanova
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Maria
authors.initials: M
authors.lastname: Lara-Tejero
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Galán
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D005260:Female; D006706:Homeostasis; D006801:Humans; D007113:Immunity, Innate; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D000069296:Type III Secretion Systems; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D016328:NF-kappa B; D000069296:Type III Secretion Systems