Genetic diversity in Treponema pallidum: implications for pathogenesis, evolution and molecular diagnostics of syphilis and yaws

Abstract

Pathogenic uncultivable treponemes, similar to syphilis-causing Treponema pallidum subspecies pallidum, include T. pallidum ssp. pertenue, T. pallidum ssp. endemicum and Treponema carateum, which cause yaws, bejel and pinta, respectively. Genetic analyses of these pathogens revealed striking similarity among these bacteria and also a high degree of similarity to the rabbit pathogen, Treponema paraluiscuniculi, a treponeme not infectious to humans. Genome comparisons between pallidum and non-pallidum treponemes revealed genes with potential involvement in human infectivity, whereas comparisons between pallidum and pertenue treponemes identified genes possibly involved in the high invasivity of syphilis treponemes. Genetic variability within syphilis strains is considered as the basis of syphilis molecular epidemiology with potential to detect more virulent strains, whereas genetic variability within a single strain is related to its ability to elude the immune system of the host. Genome analyses also shed light on treponemal evolution and on chromosomal targets for molecular diagnostics of treponemal infections.

Fig. 1

A. An unrooted tree constructed from whole genome sequence alignments using the maximum parsimony method. The bar scale corresponds to 1000 nt changes. Bootstrap values based on 1,000 replications are shown next to branches. The tree is very similar to that obtained following analysis of binary restriction target site data (Mikalová et al., 2010). B. An unrooted tree constructed from concatenated nucleotide sequences of TP0136, TP0326, TP0488, and TP0548 genes using the maximum likelihood method. The length of sequenced regions ranged from 8342 to 8412 nucleotides. The bar scale corresponds to 0.01 nt changes per site. Bootstrap values based on 1,000 replications are shown next to branches. The TPA strains cluster into two separate groups, one containing the Nichols and the second the SS14 strain. In addition to strains listed in the Table 1, TPA strains Grady, Philadelphia 1, Philadelphia 2, MN-3, and Bal-73-01 are shown.

Fig. 2

A. Genes of T. paraluiscuniculi Cuniculi A and TPE with predicted cell function with major sequence changes compared to the Nichols orthologs. Cuniculi A genes containing internal frameshifts and/or major sequence changes (Šmajs et al., 2011) and TPE genes encoding proteins with six or more amino acid changes and/or major sequence changes when compared to TPA genes (Čejková et al., 2011). B. Genes of T. paraluiscuniculi Cuniculi A and TPE with unknown function with major sequence changes compared to the Nichols orthologs. Same criteria were used as in panel A.