A type IVB secretion system contributes to the pathogenicity ofYersinia pseudotuberculosisstrains responsible for the Far East scarlet-like fever

Abstract

AbstractYersinia pseudotuberculosisis a food-borne pathogen responsible for a self-limiting gastrointestinal disease in humans known as mesenteric lymphadenitis. A phylogenetically distinctY. pseudotuberculosiscluster from lineages 1 and 8 is associated to a specific syndrome called the Far East scarlet-like fever (FESLF), characterized by skin rash, hyperemic tongue and desquamation. Genome sequencing of FESLF strains previously revealed the presence in the plasmid pVM82 ofdot/icmgenes, homologous to those known to encode a T4BSS in the intracellular pathogensLegionella pneumophilaandCoxiella burnetii.In the present article, we characterized the genomic features and functionality of theY. pseudotuberculosisT4BSS (yT4BSS). We found higherdot/icmgene identity betweenY. pseudotuberculosisandPseudomonas putidagenes than with those ofL. pneumophilaorC. burnetii. We validated the presence of all essentialdot/icmgenes required for the structure of a T4BSS. We then evaluated the conditions required foryT4BSS gene expressionin vitroand identified an influence of temperature, with higher expression at 37°C, which mimicks the mammalian host temperature. TheyT4BSS is also expressedin celluloduring theY. pseudotuberculosisintracellular life cycle andin vivoduring mouse infection. Although T4BSS functions are well characterized in the intracellular life cycle ofL. pneumophilaandC. burnetii, theyT4BSS appears to not be required for the intracellular survival nor for the establishment of a replication niche within cells ofY. pseudotuberculosis. Interestingly, theyT4BSS is implicated inY. pseudotuberculosisFESLF strain pathogenicity when orally inoculated to mice but not during intravenous inoculation. Despite a role in virulence during oral infection, theyT4BSS does not influence organ colonization. However, theyT4BSS appears to be implicated in induction of important necrosis lesions in mesenteric lymph nodes and cæca of mice. Cytokine profil analyses revealed an induction of production of innate immunity related cytokines and chemokines depending on theyT4BSSin cellulousing a mouse bone marrow-derived macrophages infection model. Thus, theyT4BSS modulates cytokine responses of the host innate immune system during oral infection. In conclusion, theyT4BSS is a newly characterized virulence factor implicated in pathogenicity ofY. pseudotuberculosisstrains from lineage 8 responsible for FESLF.