ARTHRITOGENICITY OF GENETICALLY MANIPULATED YERSINIA-ENTEROCOLITICA SEROTYPE O8 FOR LEWIS RATS

Yersinia enterocolitica strains of serotype O8 but not strains of other human pathogenic serotypes (e.g., O3 or O9) are able to induce a reactive arthritis-like disease in Lewis rats after intravenous inoculation (J. L. Hill and D. T. Yu, Infect. Immun. 55:721-726, 1987), To assess which bacterial components or pathogenic factors are crucial for arthritis induction, six genetically manipulated Y. enterocolitica 08 derivatives have been compared with the parental strain in Lewis rats. Neither differences in the length of the lipopolysaccharide side chain (smooth to semirough) of Y. enterocolitica 08 nor replacement of the virulence plasmid (pYVO8) of Y. enterocolitica O8 with that of the nonarthritogenic Y. enterocolitica O9 (pYVO9) had a significant influence on arthritogenic potential or virulence in rats. Transposon insertional inactivation of the plasmid gene yadA encoding the Yersinia adhesin and the collagen-binding protein or of the secretion of YopH resulted in decreased arthritogenicity (increase of the arthritogenic infectious dose) and pathogenicity (decreased persistence of the pathogen in spleens and livers of rats and increase of the 50% lethal dose for mice). However, mutants impaired in yersiniabactin production or uptake proved to be nonarthritogenic for rats, probably because of pronounced attenuation in virulence. From these results, we conclude that the arthritogenic potential of Y. enterocolitica serotype O8 is closely related to the virulence potential determined as the 50% lethal dose in mice and the ability to persist in lymphatic tissue of Lewis rats. A specific arthritogenic determinant of Y. enterocolitica could not be identified.