Genetics of human and animal uncultivable treponemal pathogens

Treponema pallidum is an uncultivable bacterium and the causative agent of syphilis (subsp. pallidum [TPA]), human yaws (subsp. pertenue [TPE]), and bejel (subsp. endemicum). Several species of nonhuman primates in Africa are infected by treponemes genetically undistinguishable from known human TPE strains. Besides Treponema pallidum, the equally uncultivable Treponema carateum causes pinta in humans. In lagomorphs, Treponema paraluisleporidarum ecovar Cuniculus and ecovar Lepus are the causative agents of rabbit and hare syphilis, respectively. All uncultivable pathogenic treponemes harbor a relatively small chromosome (1.1334-1.1405 Mbp) and show gene synteny with minimal genetic differences (>98% identity at the DNA level) between subspecies and species. While uncultivable pathogenic treponemes contain a highly conserved core genome, there are a number of highly variable and/or recombinant chromosomal loci. This is also reflected in the occurrence of intrastrain heterogeneity (genetic diversity within an infecting bacterial population). Molecular differences at several different chromosomal loci identified among TPA strains or isolates have been used for molecular typing and the epidemiological characterization of syphilis isolates. This review summarizes genome structure of uncultivable pathogenic treponemes including genetically variable regions.