Virulence of Yersinia pseudotuberculosis in aerosol models

Abstract

Genetic analyses have determined that Yersinia pestis and Yersinia pseudotuberculosis are so closely related that they are a single species. Transitional strains of Y. pestis (also known as Pestoides strains) are ancient strains that lie very close to Y. pseudotuberculosis in the Y. pestis lineage. We previously demonstrated that the ability to infect mice by aerosol is exhibited by the Pestoides group and that the aerosol LD 50 of these strains is comparable to that of typical isolates. In this study, we examined several Y. pseudotuberculosis strains of different serotypes in the mouse aerosol model and evaluated a subset of these in the guinea pig and rat. All of the strains of Y. pseudotuberculosis caused a fatal pneumonia in the aerosol mouse model. However, the range of virulence that we observed among natural isolates of Y. pseudotuberculosis was quite remarkable when compared to natural isolates of Y. pestis (including the Pestoides group), which have relatively uniform LD 50 values in this model. For one strain of Y. pseudotuberculosis, the toxin cytotoxic necrotizing factor (CNF) was required for aerosol virulence. However, it appears that this is strain-specific as other naturally occurring strains carrying a deletion in CNF retained virulence. In general, isolates with the high pathogenicity island were more virulent than those lacking it. In our limited testing in guinea pigs, we found a similar variability in the virulence of Y. pseudotuberculosis strains, while rats were highly resistant to aerosols of the single Y. pseudotuberculosis strain evaluated to date. Although we have observed considerable variation in the virulence of Y. pestis natural isolates by parenteral routes of infection, LD 50 values by aerosol do not vary like those of Y. pseudotuberculosis. This likely reflects the much greater genetic diversity of Y. pseudotuberculosis. A recent study indicates that gene acquisition from other species is a major factor that has influenced Y. pseudotuberculosis genome evolution. This surely played (and continues to play) a role in producing the constellation of virulence determinants observed in this organism and makes it likely that there are multiple independent mechanisms that contribute to pathogenicity by the aerosol route. © 2012 Springer Science+Business Media New York.