Whole genome sequences of three Treponema pallidum ssp. pertenue strains: yaws and syphilis treponemes differ in less than 0.2% of the genome sequence

Abstract

Background: The yaws treponemes, Treponema pallidum ssp. pertenue (TPE) strains, are closely related to syphilis causing strains of Treponema pallidum ssp. pallidum (TPA). Both yaws and syphilis are distinguished on the basis of epidemiological characteristics, clinical symptoms, and several genetic signatures of the corresponding causative agents.

Methodology/principal findings: To precisely define genetic differences between TPA and TPE, high-quality whole genome sequences of three TPE strains (Samoa D, CDC-2, Gauthier) were determined using next-generation sequencing techniques. TPE genome sequences were compared to four genomes of TPA strains (Nichols, DAL-1, SS14, Chicago). The genome structure was identical in all three TPE strains with similar length ranging between 1,139,330 bp and 1,139,744 bp. No major genome rearrangements were found when compared to the four TPA genomes. The whole genome nucleotide divergence (d(A)) between TPA and TPE subspecies was 4.7 and 4.8 times higher than the observed nucleotide diversity (π) among TPA and TPE strains, respectively, corresponding to 99.8% identity between TPA and TPE genomes. A set of 97 (9.9%) TPE genes encoded proteins containing two or more amino acid replacements or other major sequence changes. The TPE divergent genes were mostly from the group encoding potential virulence factors and genes encoding proteins with unknown function.

Conclusions/significance: Hypothetical genes, with genetic differences, consistently found between TPE and TPA strains are candidates for syphilitic treponemes virulence factors. Seventeen TPE genes were predicted under positive selection, and eleven of them coded either for predicted exported proteins or membrane proteins suggesting their possible association with the cell surface. Sequence changes between TPE and TPA strains and changes specific to individual strains represent suitable targets for subspecies- and strain-specific molecular diagnostics.

Figure 1. A schematic representation of the chromosomal TP0126 and TP0127 region.

Newly annotated genes for each TPE strain are shown in comparison with resequenced and reannotated Nichols genes. Gene names were modified according to the GenBank instructions from the previously published ones . The TP0126.1, TP0126.2, TP0126.4, and TP0126.5 genes were renamed as TP0126a, TP0126b, TP0126c and TP0126d, respectively.

Figure 2. Number of nucleotide differences consistently found between all investigated pertenue and pallidum genomes.

Differences shown in 5 kb-long intervals along the treponemal chromosome. Please note that the numbers of nucleotide changes (shown in bp) are for 7 intervals artificially terminated at 100 nt; the real values are shown next to corresponding vertical columns.