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.

Department of Biology Masaryk University Kamenice 5 Building A6 625 00 Brno Czech Republic

Work Group Neglected Tropical Diseases Pathology Unit German Primate Center Leibniz Institute for Primate Research Kellnerweg 4 37077 Göttingen Germany

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Resistance to ceftriaxone and penicillin G among contemporary syphilis strains confirmed by natural in vitro mutagenesis

Whole-genome sequencing reveals evidence for inter-species transmission of the yaws bacterium among nonhuman primates in Tanzania

Whole genome sequences of nine Taylorella equigenitalis strains isolated in the Czech Republic between 1982-2021: Molecular dating suggests a common ancestor at the time of Roman Empire

The hare syphilis agent is related to, but distinct from, the treponeme causing rabbit syphilis

Treponema pallidum subsp. pallidum strains DAL-1 and Philadelphia 1 differ in generation times in vitro as well as during experimental rabbit infection

Low genetic diversity of Treponema pallidum ssp. pertenue (TPE) isolated from patients' ulcers in Namatanai District of Papua New Guinea: Local human population is infected by three TPE genotypes

The genomes of the yaws bacterium, Treponema pallidum subsp. pertenue, of nonhuman primate and human origin are not genomically distinct

High frequency of Nichols-like strains and increased levels of macrolide resistance in Treponema pallidum in clinical samples from Buenos Aires, Argentina

Whole genome sequences of Treponema pallidum subsp. endemicum isolated from Cuban patients: The non-clonal character of isolates suggests a persistent human infection rather than a single outbreak

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Whole genome sequence of the Treponema pallidum subsp. endemicum strain Iraq B: A subpopulation of bejel treponemes contains full-length tprF and tprG genes similar to those present in T. p. subsp. pertenue strains

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First report of hare treponematosis seroprevalence of European brown hares (Lepus europaeus) in the Czech Republic: seroprevalence negatively correlates with altitude of sampling areas

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A public database for the new MLST scheme for Treponema pallidum subsp. pallidum: surveillance and epidemiology of the causative agent of syphilis

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