title: The Tat Substrate SufI Is Critical for the Ability of Yersinia pseudotuberculosis To Cause Systemic Infection.
abstract: The twin arginine translocation (Tat) system targets folded proteins across the inner membrane and is crucial for virulence in many important human-pathogenic bacteria. Tat has been shown to be required for the virulence ofYersinia pseudotuberculosis, and we recently showed that the system is critical for different virulence-related stress responses as well as for iron uptake. In this study, we wanted to address the role of the Tat substrates inin vivovirulence. Therefore, 22 genes encoding potential Tat substrates were mutated, and each mutant was evaluated in a competitive oral infection of mice. Interestingly, a ΔsufImutant was essentially as attenuated for virulence as the Tat-deficient strain. We also verified that SufI was Tat dependent for membrane/periplasmic localization inY. pseudotuberculosisIn vivobioluminescent imaging of orally infected mice revealed that both the ΔsufIand ΔtatCmutants were able to colonize the cecum and Peyer's patches (PPs) and could spread to the mesenteric lymph nodes (MLNs). Importantly, at this point, neither the ΔtatCmutant nor the ΔsufImutant was able to spread systemically, and they were gradually cleared. Immunostaining of MLNs revealed that both the ΔtatCand ΔsufImutants were unable to spread from the initial infection foci and appeared to be contained by neutrophils, while wild-type bacteria readily spread to establish multiple foci from day 3 postinfection. Our results show that SufI alone is required for the establishment of systemic infection and is the major cause of the attenuation of the ΔtatCmutant.
authors.affiliation: Department of Molecular Biology, Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden.|Department of Molecular Biology, Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden.
authors.forename: Ummehan
authors.initials: U
authors.lastname: Avican
authors.affiliation: Department of Molecular Biology, Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden.|Department of Molecular Biology, Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden.
authors.forename: Tugrul
authors.initials: T
authors.lastname: Doruk
authors.affiliation: Department of Molecular Biology, Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden.|Department of Molecular Biology, Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden.
authors.forename: Yngve
authors.initials: Y
authors.lastname: Östberg
authors.affiliation: Department of Molecular Biology, Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Fahlgren
authors.affiliation: Department of Molecular Biology, Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden ake.forsberg@umu.se.|Department of Molecular Biology, Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden.
authors.forename: Åke
authors.initials: Å
authors.lastname: Forsberg
mesh_terms: D000818:Animals; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter; D051379:Mice; D016296:Mutagenesis; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D013379:Substrate Specificity; D000069294:Twin-Arginine-Translocation System / Q000235:genetics / Q000378:metabolism*; D014774:Virulence / Q000235:genetics; D015011:Yersinia pseudotuberculosis / Q000472:pathogenicity / Q000502:physiology*; D015012:Yersinia pseudotuberculosis Infections / Q000382:microbiology*
chemical_list: D001426:Bacterial Proteins; D000069294:Twin-Arginine-Translocation System
keywords: SufI; Tat pathway; Yersinia pseudotuberculosis; mesenteric lymph nodes; neutrophils; virulence