Tracing the origin of Treponema pallidum in China using next-generation sequencing

Abstract

Syphilis is a systemic sexually transmitted disease caused by Treponema pallidum ssp. pallidum (TPA). The origin and genetic background of Chinese TPA strains remain unclear. We identified a total of 329 single-nucleotide variants (SNVs) in eight Chinese TPA strains using next-generation sequencing. All of the TPA strains were clustered into three lineages, and Chinese TPA strains were grouped in Lineage 2 based on phylogenetic analysis. The phylogeographical data showed that TPA strains originated earlier than did T. pallidum ssp. pertenue (TPE) and T. pallidum ssp. endemicum (TPN) strains and that Chinese TPA strains might be derived from recombination between Lineage 1 and Lineage 3. Moreover, we found through a homology modeling analysis that a nonsynonymous substitution (I415F) in the PBP3 protein might affect the structural flexibility of PBP3 and the binding constant for substrates based on its possible association with penicillin resistance in T. pallidum. Our findings provide new insight into the molecular foundation of the evolutionary origin of TPA and support the development of novel diagnostic/therapeutic technology for syphilis.

Reanalysis of Chinese Treponema pallidum samples: all Chinese samples cluster with SS14-like group of syphilis-causing treponemes

“…strains containing a mixed pattern of Nichols-like and SS14-like genomic sequences, have been identified. Recently, Sun et al (Oncotarget 2016 . 10.18632/oncotarget.10154) described a new “phylogenetic group” (called Lineage 2) among Chinese TPA strains.…”

Ancient bacterial genomes reveal a formerly unknown diversity ofTreponema pallidumstrains in early modern Europe

“…Midpoint-rooted ML trees of our historical European genomes, previously published colonial Mexican genomes 45 and 26 modern treponemal genomes 34,[67][68][69][70][71][72][73][74][75] were constructed for the alignment. The four ancient European genomes are placed at three distinct positions in the phylogenetic tree.…”

“…A recombination analysis was conducted as described in Arora et al 2016 34 , including 26 modern genomes 34,[67][68][69][70][71][72][73][74][75] and six ancient ones: the colonial Mexican genomes 94A, 94B, and 133 from an earlier study 45 and three of our historical European genomes, namely PD28, CHS119 and SJ219 ( Table 2). Sample KM14-7 was excluded from the recombination analysis due to its sporadic placement in the Maximum-Likelihood (ML) tree topologies, which were derived for entire genomes and for each gene individually.…”

Peer Review #2 of "A public database for the new MLST scheme for Treponema pallidum subsp. pallidum: surveillance and epidemiology of the causative agent of syphilis (v0.1)"

“…All published whole genome and draft genome sequences of TPA (Pětrošová et al, 2013;Giacani et al, 2010;Pětrošová et al, 2012;Zobaníková et al, 2012;Giacani et al, 2014;Tong et al, 2017;Arora et al, 2016;Sun et al, 2016;Pinto et al, 2016;Strouhal et al, 2018;Grillová et al 2018b), data available at GenBank, as well as sequences obtained by MLST (Grillová et al, 2018a;Pospíšilová et al, 2018) were submitted to the database.…”