2015, Vol.9(10), p.e0004110
Pathogenic uncultivable treponemes comprise human and animal pathogens including agents of syphilis, yaws, bejel, pinta, and venereal spirochetosis in rabbits and hares. A set of 10 treponemal genome sequences including those of 4 Treponema pallidum ssp. pallidum (TPA) strains (Nichols, DAL-1, Mexico A, SS14), 4 T . p . ssp. pertenue (TPE) strains (CDC-2, Gauthier, Samoa D, Fribourg-Blanc), 1 T . p . ssp. endemicum (TEN) strain (Bosnia A) and one strain (Cuniculi A) of Treponema paraluisleporidarum ecovar Cuniculus (TPLC) were examined with respect to the presence of nucleotide intrastrain heterogeneous sites. ; The number of identified intrastrain heterogeneous sites in individual genomes ranged between 0 and 7. Altogether, 23 intrastrain heterogeneous sites (in 17 genes) were found in 5 out of 10 investigated treponemal genomes including TPA strains Nichols (n = 5), DAL-1 (n = 4), and SS14 (n = 7), TPE strain Samoa D (n = 1), and TEN strain Bosnia A (n = 5). Although only one heterogeneous site was identified among 4 tested TPE strains, 16 such sites were identified among 4 TPA strains. Heterogeneous sites were mostly strain-specific and were identified in four tpr genes ( tprC , GI , I , K ), in genes involved in bacterial motility and chemotaxis ( fliI , cheC-fliY ), in genes involved in cell structure ( murC ), translation ( prfA ), general and DNA metabolism (putative SAM dependent methyltransferase, topA ), and in seven hypothetical genes. ; Heterogeneous sites likely represent both the selection of adaptive changes during infection of the host as well as an ongoing diversifying evolutionary process. ; The genus Treponema comprises several uncultivable human and animal pathogens including Treponema pallidum ssp. pallidum (TPA), the causative agent of syphilis, T . p . ssp. pertenue (TPE, the causative agent of yaws), and T . p . ssp. endemicum (TEN, the causative agent of bejel). Simian TPE strain Fribourg-Blanc and T . paraluisleporidarum , the agents of primate infections and venereal spirochetosis of rabbits and hares, respectively, represent animal pathogens. In this study, whole genome sequences of 10 treponemal strains were systematically analyzed for the presence of nucleotide sites where the treponemal strains differed within a single strain. Interestingly, most heterogeneous sites were identified among TPA and TEN strains but not among tested TPE strains. Although heterogeneous sites were found to be mostly strain-specific, several examples revealed the same heterogeneous site was identified in two genomes. These findings indicate that the number of intrastrain heterogeneous sites per genome is limited and that different treponemal strains tend to display variability in the same positions of several genes. The abundance of nonsynonymous mutations, nonconservative amino acid replacements and the fact that most of the heterogeneous sites were located within coding regions suggest that the heterogeneous sites represent beneficial adaptive mutations.