Treponemes in wild lagomorphs: Genetic diversity and relatedness to human pathogenic T. pallidum

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Bacteria of the genus Treponema are known human and animal pathogens. While human and nonhuman primate pathogenic T. pallidum has been intensively studied for decades, there is little information on the diversity, clinical relevance, and occurrence of treponemes (T. paraluisleporidarum ecovar Cuniculus (TPeCuniculus) and ecovar Lepus (TPeLepus)) that naturally infect wild rabbits and hares (lagomorphs). Infection, however, is widespread in Europe. Similar to human syphilis, lagomorph treponemal disease is typically sexually transmitted and results in erythema and edema of the anogenital area, often followed by skin ulceration and crusting of the lesion. The rabbit pathogenic treponemes are not infectious for humans despite the fact, that these treponemes show genome sequence identity with human T. pallidum higher than 98%. Therefore, an analysis focused on treponemes infecting lagomorphs will reveal not only characterization of these animal pathogens but will also help to better understand the evolution and biology of human infecting T. pallidum. There are three specific aims of the submitted project including i) testing of seroprevalence of rabbit and hare treponematoses among animals caught in the Czech Republic and in Germany as well as in other selected areas mainly in Europe, ii) analysis of strain diversity within TPeCuniculus and TPeLepus as well as its correlation with high host-specificity of these treponemes, and iii) genomic analysis of the potential evolutionary ancestry of TPeLepus. In summary, we are planning to screen over 2,000 lagomorph samples taken mostly from European animals for determination of serological status and the presence of treponemal DNA. We expect to characterize about 90 DNA-containing samples for genetic diversity through Multi-Locus Strain Typing of TPeCuniculus or TPeLepus as well as we anticipate to whole genome sequence over a dozen of newly isolated lagomorph treponemes.