title: Molecular analysis of a novel Toll/interleukin-1 receptor (TIR)-domain containing virulence protein of Y. pseudotuberculosis among Far East scarlet-like fever serotype I strains.
abstract: Pathogenicity of Yersinia pseudotuberculosis is determined by an arsenal of virulence factors. Particularly, the Yersinia outer proteins (Yops) and the Type III secretion system (T3SS) encoded on the pYV virulence plasmid are required for Yersinia pathogenicity. A specific group of Y. pseudotuberculosis, responsible for the clinical syndrome described as Far East scarlet-like fever (FESLF), is known to have an altered virulence gene cluster. Far East strains cause unique clinical symptoms for which the pYV virulence plasmid plays apparently a rather secondary role. Here, we characterize a previously unknown protein of Y. pseudotuberculosis serotype I strains (TcpYI) which can be found particularly among the FESLF strain group. The TcpYI protein shares considerable sequence homology to members of the Toll/IL-1 receptor family. Bacterial TIR domain containing proteins (Tcps) interact with the innate immune system by TIR-TIR interactions and subvert host defenses via individual, multifaceted mechanisms. In terms of virulence, it appears that the TcpYI protein of Y. pseudotuberculosis displays its own virulence phenotype compared to the previously characterized bacterial Tcps. Our results clearly demonstrate that TcpYI increases the intracellular survival of the respective strains in vitro. Furthermore, we show here that the intracellular survival benefit of the wild-type strain correlates with an increase in tcpYI gene expression inside murine macrophages. In support of this, we found that TcpYI enhances the survival inside the spleens of mice in a mouse model of peritonitis. Our results may point toward involvement of the TcpYI protein in inhibition of phagocytosis, particularly in distinct Y. pseudotuberculosis strains of the FESLF strain group where the pYV virulence plasmid is absent.
authors.affiliation: Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Marchioninistr. 17, D-81377 München, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Nörenberg
authors.forename: Andreas
authors.initials: A
authors.lastname: Wieser
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Magistro
authors.forename: Christiane
authors.initials: C
authors.lastname: Hoffmann
authors.forename: Christian
authors.initials: C
authors.lastname: Meyer
authors.forename: Maxim
authors.initials: M
authors.lastname: Messerer
authors.forename: Sören
authors.initials: S
authors.lastname: Schubert
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050296:Microbial Viability; D010538:Peritonitis / Q000382:microbiology; D013154:Spleen / Q000382:microbiology; D037521:Virulence Factors / Q000235:genetics* / Q000378:metabolism; D015009:Yersinia Infections / Q000382:microbiology*; D015011:Yersinia pseudotuberculosis / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology*
chemical_list: D037521:Virulence Factors
keywords: FESLF; Far East scarlet-like fever; Phagocytosis; TIR domain protein; Toll/interleukin-1 receptor family; Yersinia pseudotuberculosis