title: YopP-expressing variant of Y. pestis activates a potent innate immune response affording cross-protection against yersiniosis and tularemia [corrected].
abstract: Plague, initiated by Yersinia pestis infection, is a rapidly progressing disease with a high mortality rate if not quickly treated. The existence of antibiotic-resistant Y. pestis strains emphasizes the need for the development of novel countermeasures against plague. We previously reported the generation of a recombinant Y. pestis strain (Kim53ΔJ+P) that over-expresses Y. enterocolitica YopP. When this strain was administered subcutaneously to mice, it elicited a fast and effective protective immune response in models of bubonic, pneumonic and septicemic plague. In the present study, we further characterized the immune response induced by the Kim53ΔJ+P recombinant strain. Using a panel of mouse strains defective in specific immune functions, we observed the induction of a prompt protective innate immune response that was interferon-γ dependent. Moreover, inoculation of mice with Y. pestis Kim53ΔJ+P elicited a rapid protective response against secondary infection by other bacterial pathogens, including the enteropathogen Y. enterocolitica and the respiratory pathogen Francisella tularensis. Thus, the development of new therapies to enhance the innate immune response may provide an initial critical delay in disease progression following the exposure to highly virulent bacterial pathogens, extending the time window for successful treatment.
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel.
authors.forename: Ayelet
authors.initials: A
authors.lastname: Zauberman
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Flashner
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel.
authors.forename: Yinon
authors.initials: Y
authors.lastname: Levy
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel.
authors.forename: Yaron
authors.initials: Y
authors.lastname: Vagima
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel.
authors.forename: Avital
authors.initials: A
authors.lastname: Tidhar
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Cohen
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel.
authors.forename: Erez
authors.initials: E
authors.lastname: Bar-Haim
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Gur
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel.
authors.forename: Moshe
authors.initials: M
authors.lastname: Aftalion
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel.
authors.forename: Gideon
authors.initials: G
authors.lastname: Halperin
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel.
authors.forename: Avigdor
authors.initials: A
authors.lastname: Shafferman
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel.
authors.forename: Emanuelle
authors.initials: E
authors.lastname: Mamroud
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D056738:Cross Protection / Q000235:genetics / Q000276:immunology; D005260:Female; D005604:Francisella tularensis / Q000276:immunology; D014644:Genetic Variation; D007113:Immunity, Innate / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010930:Plague / Q000276:immunology* / Q000517:prevention & control; D010931:Plague Vaccine / Q000276:immunology; D014406:Tularemia / Q000276:immunology* / Q000517:prevention & control; D015009:Yersinia Infections / Q000276:immunology; D015010:Yersinia pestis / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; D010931:Plague Vaccine; C118802:Yop proteins translocation protein P, Yersinia