ROLE OF YADA IN ARTHRITOGENICITY OF YERSINIA-ENTEROCOLITICA SEROTYPE O-8 - EXPERIMENTAL STUDIES WITH RATS

Outer membrane protein YadA, the Yersinia adhesin, is one of the plasm id-encoded virulence factors of yersiniae. To evaluate the role of Yad A in the pathogenesis of reactive arthritis experimentally, we used Ya dA(-) strain YeO8-116, a kanamycin GenBlock insertion mutant derived f rom Yersinia enterocolitica O:8 wild-type strain 8081. As control stra ins, a plasmid-cured derivative (8081-c) of 8081 and a YopH(-) mutant (8081-yoph) were used. In addition, YeO8-116, with the yadA mutation t ranscomplemented with plasmid pMW10, was used. YeO8-116 induced arthri tis to a considerably lesser extent than did wild-type strain 8081 whe n inoculated intravenously into Lewis rats. In rats surviving for over 14 days after the bacterial inoculation, the arthritis incidences wer e 6% (4 of 72) among those inoculated with the yadA mutant and 51% (33 of 65) among those inoculated with wild-type strain 8081. When the ya dA gene was transcomplemented back to YeO8-116, YeO8-116/pMW10 induced arthritis in 47% (9 of 19) of the inoculated rats. Plasmid-cured stra in 8081-c did not induce arthritis in any of the 24 inoculated rats, w hereas YopH(-) mutant 8081-yoph induced arthritis in 20% (5 of 25) of the rats inoculated. Although the 50% lethal dose of YeO8-116 was abou t sixfold higher than that of 8081, the kinetics of bacterial eliminat ion from the spleen and mesenteric lymph nodes were about the same wit h both strains. Antibody responses in rats infected with the two strai ns were also indistinguishable. Our results indicate that YadA contrib utes to the arthritogenicity of Y. enterocolitica in the rat model.