We attempted to induce experimental arthritis in rats by systematically testing the effect of Yersinia infections in five strains of rats, using the intragastric, intraperitoneal, and intravenous routes of inoculation. We observed that Lewis rats which were given 104 to 105 Yersinia enterocolitica WA organisms via the intravenous route consistently developed arthritis. The arthritis was most severe at 3 weeks and subsided at 6 weeks. No arthritis was observed when this bacterial strain was administered to Buffalo, Fisher, DA, and LDA rats. No replicable bacteria were detected in the joints. This aseptic characteristic parallels that seen in the human condition and establishes this as an animal model of Yersinia-induced arthritis. The probable reason for arthritis development in only the Lewis rats became apparent when we analyzed the numbers of live bacteria in the spleens and livers of these infected animals. The arthritis-susceptible Lewis rats harbored 10-fold more bacteria than the arthritis-resistant rat strains, and this systemic infection also persisted for a significantly longer period. Speculations as to why human subjects who develop Yersinia-induced arthritis are genetically predisposed have been centered principally around the role of the HLA-B27 histocompatibility antigens. The present study reveals a heretofore unrecognized critical factor: the susceptibility of the hosts to the virulence of the infectious organisms. In addition, the present animal model will provide the necessary tool for the investigation of this and other important host and bacterial factors.
The outer membranes of gram-negative bacteria are considered to be of importance in host-bacteria interaction, in protective immunity, and occasionally in subclassification within a species. In this study, the outer membranes of several strains of Yersinia enterocolitica and Y. pseudotuberculosis were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). It was found that the appearance of the major proteins depended on the temperature at which they were solubilized in SDS. A protein was identified with the use of two-dimensional gels and preparative SDS-PAGE, which was equivalent to the "heat-modifiable protein" (protein II) of other Enterobacteriaceae species. A monoclonal antibody, 4G1, was generated against an isolated preparation of this Y. enterocolitica protein. This antibody was tested with whole cell bacterial antigens of 46 individual bacterial strains. The reactive strains included only Y. enterocolitica and Y. pseudotuberculosis. In addition, the reactivity of the 4G1 monoclonal antibody preparation could be absorbed only with Y. enterocolitica and Y. pseudotuberculosis, and not with other strains of bacteria. The reactivity of this 4G1 monoclonal antibody was also tested by the Western Blot technique. Six individual strains were tested: a Y. enterocolitica serotype 0:3, a Y. enterocolitica serotype 0:9, an Escherichia coli, a Salmonella typhimurium, a Shigella flexneri, and a Klebsiella pneumoniae. The 4G1 antibody reacted with only the proteins of the two Y. enterocolitica strains. In conclusion, the equivalent of the heat-modifiable protein was present in Y. enterocolitica and Y. pseudotuberculosis. Moreover, this protein also carried a species-specific antigenic determinant.
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