Whole genome sequencing of the agent of yaws isolated from nonhuman primates and humans
Introduction
Treponema pallidum subsp. pertenue (TPE) is the causative agent of human disease yaws. Yaws is currently reported in 16 endemic countries in Africa, southern Asia, and the Pacific region. First yaws eradication effort during the mid-20th century resulted in a global 95% drop in the disease prevalence, but the lack of continued surveillance has led to its resurgence. A development of a second, currently ongoing yaws eradication campaign was supported by the development of new simple and effective treatment. The disease was believed to have no animal reservoirs, but evidence of similar disease in wild populations of non-human primates (NHPs) in sub-Saharan Africa started to appear since 1960s. Genetic evidence showed a high similarity to human TPE, and this discovery opened the question of the bacterium’s identity and possibilities of its transmission between NHPs and humans.
Methods
Collected samples of strains originating from NHPs in Tanzania have been sequenced and their genomes analysed and compared. Further comparison with human TPE strains included in-depth analyses of trp genes, length of homopolymeric tracts, rrn operon variants, number of repetitions in genes TP0304, TP0433, TP0470, IGR TP0488-9 and TP0967 and phylogenetic analyses. Substitution rate has also been calculated.
Results
The bacteria isolated from four species of NHPs, collected from three national parks in Tanzania, were sequenced. In total, eight complete whole genome sequences of NHP strains were determined, with additional thirteen draft whole genome sequences. Previously undetermined chromosomal regions (sequencing gaps), that prevented the researches from making a conclusion regarding the sequence identity of TPE genomes originating from NHPs and humans, were resolved. The comparison among genome sequences revealed no consistent differences between human and NHP TPE genomes. When the NHP TPE genomes were compared with each other, five combinations of genome-to-genome comparisons revealed an unexpectedly high degree of genetic similarity in samples collected from different NHP species, consistent with inter-species transmission of TPE among NHPs. The substitution rate of TPE of NHP origin was estimated to range between 1.77×10-7 and 3.43×10-7 per genomic site per year.
Conclusion
The data show that NHPs are infected with strains that are not only similar to the strains infecting humans but are genomically indistinguishable from them. The model estimations predicted that the inter-species transmission in NHPs happened recently, within decades. Moreover, the geographical separation of the sampling sites does not preclude TPE transmission between and within NHP species.