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

密螺旋体属细菌是已知的人类和动物病原体。虽然人类和非人类灵长类致病性梅毒螺旋体已经被深入研究了几十年，但关于自然感染野兔和野兔的密螺旋体（T. paruisleporidarum ecovar Cuniculus （TPeCuniculus）和ecovar Lepus (TPeLepus)）的多样性、临床相关性和发生率的信息很少。然而，感染在欧洲很普遍。与人类梅毒类似，梅毒螺旋体lagomorph通常是性传播的，导致肛门生殖器区域的红斑和水肿，通常随后是皮肤溃疡和病变的结痂。兔致病性密螺旋体对人类不具有传染性，尽管这些密螺旋体的基因组序列与人类苍白体的同源性高于98%。因此，对密螺旋体感染lagomorphs的分析不仅将揭示这些动物病原体的特征，而且将有助于更好地了解人类感染T. pallidum的进化和生物学。提交的项目有三个具体目标，包括1)在捷克共和国和德国以及主要在欧洲其他选定地区捕获的动物中检测兔和兔密螺旋体病的血清患病率，2)分析TPeCuniculus和TPeLepus的菌株多样性及其与这些密螺旋体高宿主特异性的相关性，以及3)对TPeLepus潜在进化祖先的基因组分析。总之，我们计划筛选2000多份主要来自欧洲动物的lagomorph样本，以确定血清学状态和密螺旋体DNA的存在。我们期望通过TPeCuniculus或TPeLepus的多位点菌株分型来表征约90个含dna样本的遗传多样性，并期望对十几种新分离的lagomorph密螺旋体进行全基因组测序。

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.