PATHOGENESIS OF DEFINED INVASION MUTANTS OF YERSINIA-ENTEROCOLITICA IN A BALB C MOUSE MODEL OF INFECTION/

It has been hypothesized for many years that the ability of Yersinia s pp. to invade tissue culture cells is reflective of their ability to p enetrate the intestinal epithelium and that this capacity is an import ant aspect of the disease process. Three different genes from Yersinia spp. that are involved in the tissue culture invasion phenotype have been identified: inv, ail, and yadA. It was previously shown that inv is necessary for efficient penetration of the intestinal epithelium by Yersinia enterocolitica. The present study was initiated to determine whether other known Yersinia invasion factors could promote uptake of the bacteria by mice in the absence of invasin. In addition, the role s of these three invasion factors in the survival of the bacteria, let hality for mice, and development of pathology were compared. We found that YadA is necessary for persistence of Y. enterocolitica in Peyer's patches, and consistent with this observation, the yadA mutant was av irulent for mice infected either orally or intraperitoneally. In addit ion, the inv yadA double mutant was avirulent. Histological and immuno histological examination of the Peyer's patches of infected mice indic ated that despite the presence of large numbers of CFU at 24 h the yad A and ail yadA mutants cause only minimal pathology and recruitment of macrophages. At 42 h postinfection, Peyer's patches from mice infecte d with the inv mutant showed no pathology, despite the prediction that some of the mice by this time would be colonized. However, at 72 h, i nflammation and necrosis were evident in some Peyer's patches. Togethe r, these observations suggest that for visible pathology to develop, a threshold number of bacteria (>10(5)) is needed and the bacteria need to persist for more than 24 h. Lastly, YadA but not Ail may play a ro le in the less efficient, delayed invasion of the intestinal epitheliu m observed for the inv mutant.