Evolutionary Processes in the Emergence and Recent Spread of the Syphilis Agent,Treponema pallidum

Abstract

The incidence of syphilis has risen worldwide in the last decade in spite of being an easily treated infection. The causative agent of this sexually transmitted disease is the bacterium Treponema pallidum subspecies pallidum (TPA), very closely related to subsp. pertenue (TPE) and endemicum (TEN), responsible for the human treponematoses yaws and bejel, respectively. Although much focus has been placed on the question of the spatial and temporary origins of TPA, the processes driving the evolution and epidemiological spread of TPA since its divergence from TPE and TEN are not well understood. Here, we investigate the effects of recombination and selection as forces of genetic diversity and differentiation acting during the evolution of T. pallidum subspecies. Using a custom-tailored procedure, named phylogenetic incongruence method, with 75 complete genome sequences, we found strong evidence for recombination among the T. pallidum subspecies, involving 12 genes and 21 events. In most cases, only one recombination event per gene was detected and all but one event corresponded to intersubspecies transfers, from TPE/TEN to TPA. We found a clear signal of natural selection acting on the recombinant genes, which is more intense in their recombinant regions. The phylogenetic location of the recombination events detected and the functional role of the genes with signals of positive selection suggest that these evolutionary processes had a key role in the evolution and recent expansion of the syphilis bacteria and significant implications for the selection of vaccine candidates and the design of a broadly protective syphilis vaccine.

Syphilitic Folliculitis: A Case Report With Demonstration of Spirochetes Showing Follicular Epitheliotropism

“…20 The importance of the function of OMPs is supported by genetic studies showing that a majority of recombination events and genomic changes in contemporary syphilitic agents involve surface-exposed antigens. 21,22 The follicular epitheliotropic identification of spirochetes in this patient, therefore, is likely related to the above discussed factors.…”

Evidente—a visual analytics tool for data enrichment in SNP-based phylogenetic trees

“…The data of the second use-case consists of 75 T. pallidum samples with a total of 2550 different SNP positions ( Pla-Díaz et al , 2022 ). In addition, we used metadata regarding the antibiotic resistance of some samples against the macrolide azithromycin ( Arora et al , 2016 ) as well as geographical origin, year of isolation and subspecies classification (TPA, TPE or TEN).…”

“…Finally, to demonstrate how Evidente can be used to fulfill task T 4 , the clade SS14 of T.pallidum was analyzed to identify enriched GO-terms within the clade. The GFF annotation file of the Nichols strain (RefSeq NC_021490) was used, since this reference genome was used to compute the SNP-table ( Pla-Díaz et al , 2022 ). The GO-term IDs related to the coding genes were predicted using FACoP ( http://facop.molgenrug.nl/ ).…”

A suite of PCR-LwCas13a assays for detection and genotyping of Treponema pallidum in clinical samples

“…S6b), respectively, the genotyping assay is expected to have robust specificity for TPA. Recombination events have been documented to occur in the tp0548 locus of T. pallidum subspecies 57,58 . These recombination events might negatively impact the ability of the PCR-LwCas13a assay to distinguish clades in rare cases.…”