A putative type IVB secretion system contributes to the pathogenicity of Yersinia pseudotuberculosis lineage 8 strains associated to the Far East scarlet-like fever

Abstract Yersinia pseudotuberculosis is a food-borne pathogen responsible for a self-limiting mesenteric lymphadenitis. Y. pseudotuberculosis lineages 1 and 8 are also associated to the Far East scarlet-like fever (FESLF) syndrome, characterized by skin rash, hyperemic tongue and desquamation. Genome sequencing of lineage 8 FESLF strains previously revealed the presence in the plasmid pVM82 of dot/icm genes, homologous to those known to encode a Type 4B Secretion System (T4BSS) in the intracellular pathogens Legionella pneumophila and Coxiella burnetii. We validated the presence of all essential dot/icm genes required for the structure of a T4BSS and we identified acidic pH and 37°C as the main signals triggering yT4BSS expression. Putative yT4BSS effectors were also identified using the S4TE algorithm but their secretion was not confirmed in the studied conditions. The yT4BSS is also expressed in epithelial and macrophages as well as in vivo during mouse infection, but it is not required for bacterial intracellular survival. Nevertheless, the yT4BSS is implicated in Y. pseudotuberculosis FESLF pathogenicity in mice when bacteria are orally inoculated. The yT4BSS does not influence organ colonization and is rather implicated in the induction of important necrosis lesions in mesenteric lymph nodes and ceca of mice. Cytokine profile analyses in mouse bone marrow-derived macrophages revealed a yT4BSS-dependent induction of innate immunity related cytokines and chemokines. In conclusion, we identify the yT4BSS as a virulence factor of Y. pseudotuberculosis strains from lineage 8 responsible for FESLF which modulates cytokine responses of the host innate immune system.