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.

• Klíčová slova
• genome analysis, phylogenetic congruence, recombination, selection, treponematoses,
• MeSH
• frambézie * mikrobiologie   MeSH
• fylogeneze MeSH
• infekce bakteriemi rodu Treponema * mikrobiologie   MeSH
• lidé MeSH
• syfilis * epidemiologie   mikrobiologie   MeSH
• Treponema pallidum genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Syphilis is an important public health problem and an increasing incidence has been noted in recent years. Characterization of strain diversity through molecular data plays a critical role in the epidemiological understanding of this re-emergence. We here propose a new high-resolution multilocus sequence typing (MLST) scheme for Treponema pallidum subsp. pallidum (TPA). We analyzed 30 complete and draft TPA genomes obtained directly from clinical samples or from rabbit propagated strains to identify suitable typing loci and tested the new scheme on 120 clinical samples collected in Switzerland and France. Our analyses yielded three loci with high discriminatory power: TP0136, TP0548, and TP0705. Together with analysis of the 23S rRNA gene mutations for macrolide resistance, we propose these loci as MLST for TPA. Among clinical samples, 23 allelic profiles as well as a high percentage (80% samples) of macrolide resistance were revealed. The new MLST has higher discriminatory power compared to previous typing schemes, enabling distinction of TPA from other treponemal bacteria, distinction between the two main TPA clades (Nichols and SS14), and differentiation of strains within these clades.

• MeSH
• alely MeSH
• antibakteriální látky farmakologie   MeSH
• DNA bakterií genetika   MeSH
• fylogeneze MeSH
• genom bakteriální MeSH
• genotyp MeSH
• globus pallidus MeSH
• jednonukleotidový polymorfismus MeSH
• makrolidy farmakologie   MeSH
• multilokusová sekvenční typizace metody   MeSH
• RNA ribozomální 23S genetika   MeSH
• sekvenční analýza DNA metody   MeSH
• syfilis epidemiologie   MeSH
• Treponema pallidum genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Francie epidemiologie   MeSH
• Švýcarsko epidemiologie   MeSH
• Názvy látek
• antibakteriální látky MeSH
• DNA bakterií MeSH
• makrolidy MeSH
• RNA ribozomální 23S MeSH

The abrupt onslaught of the syphilis pandemic that started in the late fifteenth century established this devastating infectious disease as one of the most feared in human history1. Surprisingly, despite the availability of effective antibiotic treatment since the mid-twentieth century, this bacterial infection, which is caused by Treponema pallidum subsp. pallidum (TPA), has been re-emerging globally in the last few decades with an estimated 10.6 million cases in 2008 (ref. 2). Although resistance to penicillin has not yet been identified, an increasing number of strains fail to respond to the second-line antibiotic azithromycin3. Little is known about the genetic patterns in current infections or the evolutionary origins of the disease due to the low quantities of treponemal DNA in clinical samples and difficulties in cultivating the pathogen4. Here, we used DNA capture and whole-genome sequencing to successfully interrogate genome-wide variation from syphilis patient specimens, combined with laboratory samples of TPA and two other subspecies. Phylogenetic comparisons based on the sequenced genomes indicate that the TPA strains examined share a common ancestor after the fifteenth century, within the early modern era. Moreover, most contemporary strains are azithromycin-resistant and are members of a globally dominant cluster, named here as SS14-Ω. The cluster diversified from a common ancestor in the mid-twentieth century subsequent to the discovery of antibiotics. Its recent phylogenetic divergence and global presence point to the emergence of a pandemic strain cluster.

• MeSH
• antibakteriální látky farmakologie   MeSH
• azithromycin farmakologie   MeSH
• bakteriální léková rezistence MeSH
• celosvětové zdraví MeSH
• DNA bakterií chemie   genetika   izolace a purifikace   MeSH
• fylogeneze MeSH
• genetická variace * MeSH
• genom bakteriální MeSH
• genotyp * MeSH
• lidé MeSH
• molekulární epidemiologie MeSH
• molekulární evoluce MeSH
• pandemie * MeSH
• sekvenční analýza DNA MeSH
• syfilis epidemiologie   mikrobiologie   MeSH
• Treponema pallidum klasifikace   genetika   izolace a purifikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky MeSH
• azithromycin MeSH
• DNA bakterií MeSH