Syphilis, caused by Treponema pallidum subsp. pallidum (TPA), remains an important public health problem with an increasing worldwide prevalence. Despite recent advances in in vitro cultivation, genetic variability of this pathogen during infection is poorly understood. Here, we present contemporary and geographically diverse complete treponemal genome sequences isolated directly from patients using a methyl-directed enrichment prior to sequencing. This approach reveals that approximately 50% of the genetic diversity found in TPA is driven by inter- and/or intra-strain recombination events, particularly in strains belonging to one of the defined genetic groups of syphilis treponemes: Nichols-like strains. Recombinant loci were found to encode putative outer-membrane proteins and the recombination variability was almost exclusively found in regions predicted to be at the host-pathogen interface. Genetic recombination has been considered to be a rare event in treponemes, yet our study unexpectedly showed that it occurs at a significant level and may have important impacts in the biology of this pathogen, especially as these events occur primarily in the outer membrane proteins. This study reveals the existence of strains with different repertoires of surface-exposed antigens circulating in the current human population, which should be taken into account during syphilis vaccine development.

AP HP Service de Dermatologie et Vénéréologie Groupe Hospitalier Paris Centre Cochin Hôtel Dieu Broca Paris France

Biology of Spirochetes Unit Institut Pasteur Paris France

CEITEC Central European Institute of Technology Masaryk University Brno Czechia

Central Clinical School Monash University Melbourne VIC Australia

Department of Biology Faculty of Medicine Masaryk University Brno Czechia

Department of Biology San Diego State University San Diego CA United States

Department of Dermatovenerology University Hospital Brno Brno Czechia

Department of Global Health Harborview Medical Center University of Washington Seattle WA United States

Department of Immunology Veterinary Research Institute Brno Czechia

Department of Medicine Division of Allergy and Infectious Diseases University of Washington Seattle WA United States

Department of Mycology Bacteriology Instituto de Medicina Tropical Pedro Kourí Havana Cuba

Faculté de Médecine Laboratoire de Dermatologie CNR IST Bactériennes Institut Cochin U1016 Université Sorbonne Paris Descartes Paris France

GeneticPrime Dx Inc La Jolla CA United States

Melbourne Sexual Health Centre Alfred Health Melbourne VIC Australia

National Centre for Biomolecular Research Faculty of Science Masaryk University Brno Czechia

Plateforme de Cristallographie Institut Pasteur Paris France

Zurich Institute of Forensic Medicine University of Zurich Zurich Switzerland

See more in PubMed

Andrews S. (2010). FastQC A Quality Control tool for High Throughput Sequence Data. Available at: http://www.bioinformatics.babraham.ac.uk/projects/fastqc/ (accessed June 09, 2018).

Arora N., Schuenemann V. J., Jäger G., Peltzer A., Seitz A., Herbig A., et al. (2016). Origin of modern syphilis and emergence of a pandemic Treponema pallidum cluster. Nat. Microbiol. 2:16245. 10.1038/nmicrobiol.2016.245 PubMed DOI

Bandelt H. J., Forster P., Röhl A. (1999). Median-joining networks for inferring intraspecific phylogenies. Mol. Biol. Evol. 16 37–48. 10.1093/oxfordjournals.molbev.a026036 PubMed DOI

Bankevich A., Nurk S., Antipov D., Gurevich A. A., Dvorkin M., Kulikov A. S., et al. (2012). SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J. Comput. Biol. 19 455–477. 10.1089/cmb.2012.0021 PubMed DOI PMC

Barnes H. E., Liu G., Weston C. Q., King P., Pham L. K., Waltz S., et al. (2014). Selective microbial genomic DNA isolation using restriction endonucleases. PLoS One 9:e109061. 10.1371/journal.pone.0109061 PubMed DOI PMC

Bolger A. M., Lohse M., Usadel B. (2014). Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30 2114–2120. 10.1093/bioinformatics/btu170 PubMed DOI PMC

Breese M. R., Liu Y. (2013). NGSUtils: a software suite for analyzing and manipulating next-generation sequencing datasets. Bioinformatics 29 494–496. 10.1093/bioinformatics/bts731 PubMed DOI PMC

Brinkman M. B., McGill M. A., Pettersson J., Rogers A., Matejkova P., Šmajs D., et al. (2008). A novel Treponema pallidum antigen, TP0136, is an outer membrane protein that binds human fibronectin. Infect. Immun. 76 1848–1857. 10.1128/IAI.01424-07 PubMed DOI PMC

Broad Institute (2015). Picard Toolkit. Available at: http://broadinstitute.github.io/picard/ (accessed October 24, 2018).

Bushnell B. (2017). BBMap. Available at: sourceforge.net/projects/bbmap/ (accessed May 25, 2017).

Camacho C., Coulouris G., Avagyan V., Ma N., Papadopoulos J., Bealer K., et al. (2009). BLAST+: architecture and applications. BMC Bioinformatics 10:421. 10.1186/1471-2105-10-421 PubMed DOI PMC

Čejková D., Zobaníková M., Chen L., Pospíšilová P., Strouhal M., Qin X., et al. (2012). Whole genome sequences of three Treponema pallidum ssp. Pertenue strains: yaws and syphilis treponemes differ in less than 0.2% of the genome sequence. PLoS Negl. Trop. Dis. 6:e1471. 10.1371/journal.pntd.0001471 PubMed DOI PMC

Čejková D., Zobaníková M., Pospísilová P., Strouhal M., Mikalová L., Weinstock G. M., et al. (2013). Structure of rrn operons in pathogenic non-cultivable treponemes: sequence but not genomic position of intergenic spacers correlates with classification of Treponema pallidum and Treponema paraluiscuniculi strains. J. Med. Microbiol. 62(Pt 2) 196–207. 10.1099/jmm.0.050658-0 PubMed DOI PMC

Centurion-Lara A., Giacani L., Godornes C., Molini B. J., Brinck Reid T., Lukehart S. A. (2013). Fine analysis of genetic diversity of the tpr gene family among treponemal species, subspecies and strains. PLoS Negl. Trop. Dis. 7:e2222. 10.1371/journal.pntd.0002222 PubMed DOI PMC

Centurion-Lara A., Sun E. S., Barrett L. K., Castro C., Lukehart S. A., Van Voorhis W. C. (2000). Multiple alleles of Treponema pallidum repeat gene D in Treponema pallidum isolates. J. Bacteriol. 182 2332–2335. 10.1128/jb.182.8.2332-2335.2000 PubMed DOI PMC

Chi K.-H., Danavall D., Taleo F., Pillay A., Ye T., Nachamkin E., et al. (2015). Molecular differentiation of Treponema pallidum subspecies in skin ulceration clinically suspected as yaws in Vanuatu using real-time multiplex PCR and serological methods. Am. J. Trop. Med. Hyg. 92 134–138. 10.4269/ajtmh.14-0459 PubMed DOI PMC

Cingolani P., Platts A., Wang L. L., Coon M., Nguyen T., Wang L., et al. (2012). A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3. Fly 6 80–92. 10.4161/fly.19695 PubMed DOI PMC

Dubourg G., Edouard S., Prudent E., Fournier P.-E., Raoult D. (2015). Incidental syphilis diagnosed by real-time PCR screening of urine samples. J. Clin. Microbiol. 53 3707–3708. 10.1128/jcm.01026-15 PubMed DOI PMC

Edmondson D. G., Hu B., Norris S. J. (2018). Long-Term In Vitro culture of the syphilis spirochete Treponema pallidum subsp. pallidum. mBio 9:e01153-18. 10.1128/mBio.01153-18 PubMed DOI PMC

Flasarová M., Pospíšilová P., Mikalová L., Vališová Z., Dastychová E., Strnadel R., et al. (2012). Sequencing-based molecular typing of treponema pallidum strains in the Czech Republic: all identified genotypes are related to the sequence of the SS14 strain. Acta. Derm. Venereol. 92 669–674. 10.2340/00015555-1335 PubMed DOI

Fraser C. M., Norris S. J., Weinstock G. M., White O., Sutton G. G., Dodson R., et al. (1998). Complete genome sequence of Treponema pallidum, the syphilis spirochete. Science 281 375–388. 10.1126/science.281.5375.375 PubMed DOI

Gallo Vaulet L., Grillová L., Mikalová L., Casco R., Rodríguez Fermepin M., Pando M. A., et al. (2017). Molecular typing of Treponema pallidum isolates from Buenos Aires, Argentina: frequent nichols-like isolates and low levels of macrolide resistance. PLoS One 12:e0172905. 10.1371/journal.pone.0172905 PubMed DOI PMC

Garrison E. (2016). Vcflib, A Simple C++ Library for Parsing and Manipulating VCF files. Available at: https://github.com/vcflib/vcflib (accessed July 28, 2016).

Garrison E., Marth G. (2012). Haplotype-Based Variant Detection from Short-Read Sequencing. Available from: http://arxiv.org/abs/1207.3907 (accessed October 24, 2018).

Giacani L., Iverson-Cabral S. L., King J. C. K., Molini B. J., Lukehart S. A., Centurion-Lara A. (2014). Complete genome sequence of the Treponema pallidum subsp. pallidum Sea81-4 Strain. Genome Announc. 2:e0333-14. 10.1128/genomeA.00333-14 PubMed DOI PMC

Giacani L., Jeffrey B. M., Molini B. J., Le H. T., Lukehart S. A., Centurion-Lara A., et al. (2010). Complete genome sequence and annotation of the Treponema pallidum subsp. pallidum Chicago strain. J. Bacteriol. 192 2645–2646. 10.1128/JB.00159-10 PubMed DOI PMC

Gordon A. (2014). FASTX-Toolkit: FASTQ/A Short-Reads Pre-Processing Tools. Available at: http://hannonlab.cshl.edu/fastx_toolkit/ (accessed November 29, 2016).

Gray R. R., Mulligan C. J., Molini B. J., Sun E. S., Giacani L., Godornes C., et al. (2006). Molecular evolution of the tprC, D, I, K, G, and J genes in the pathogenic genus Treponema. Mol. Biol. Evol. 23 2220–2233. 10.1093/molbev/msl092 PubMed DOI

Grillová L., Bawa T., Mikalová L., Gayet-Ageron A., Nieselt K., Strouhal M., et al. (2018a). Molecular characterization of Treponema pallidum subsp. pallidum in Switzerland and France with a new multilocus sequence typing scheme. PLoS One 13:e0200773. 10.1371/journal.pone.0200773 PubMed DOI PMC

Grillová L., Giacani L., Mikalová L., Strouhal M., Strnadel R., Marra C., et al. (2018b). Sequencing of Treponema pallidum subsp. pallidum from isolate UZ1974 using anti-treponemal antibodies enrichment: first complete whole genome sequence obtained directly from human clinical material. PLoS One 13:e0202619. 10.1371/journal.pone.0202619 PubMed DOI PMC

Grillová L., Noda A. A., Lienhard R., Blanco O., Rodríguez I., Šmajs D. (2018c). Multilocus sequence typing of Treponema pallidum subsp. pallidum in Cuba from 2012 to 2017. J. Infect. Dis. 219 1138–1145. 10.1093/infdis/jiy604 PubMed DOI

Grillová L., Jolley K., Šmajs D., Picardeau M. (2019). A public database for the new MLST scheme for Treponema pallidum subsp. Pallidum: surveillance and epidemiology of the causative agent of syphilis. PeerJ 6:e6182. 10.7717/peerj.6182 PubMed DOI PMC

Grillová L., Petrošová H., Mikalová L., Strnadel R., Dastychová E., Kuklová I., et al. (2014). Molecular typing of Treponema pallidum in the Czech Republic during 2011 to 2013: increased prevalence of identified genotypes and of isolates with macrolide resistance. J. Clin. Microbiol. 52 3693–3700. 10.1128/JCM.01292-14 PubMed DOI PMC

Gurevich A., Saveliev V., Vyahhi N., Tesler G. (2013). QUAST: quality assessment tool for genome assemblies. Bioinformatics 29 1072–1075. 10.1093/bioinformatics/btt086 PubMed DOI PMC

Harper K. N., Ocampo P. S., Steiner B. M., George R. W., Silverman M. S., Bolotin S., et al. (2008). On the origin of the treponematoses: a phylogenetic approach. PLoS Negl. Trop. Dis. 2:e148. 10.1371/journal.pntd.0000148 PubMed DOI PMC

Knauf S., Gogarten J. F., Schuenemann V. J., De Nys H. M., Düx A., Strouhal M., et al. (2018). Nonhuman primates across sub-Saharan Africa are infected with the yaws bacterium Treponema pallidum subsp. pertenue. Emerg. Microbes Infect. 7:157. PubMed PMC

Kumar S., Caimano M. J., Anand A., Dey A., Hawley K. L., LeDoyt M. E., et al. (2018). Sequence variation of rare outer membrane protein β-barrel domains in clinical strains provides insights into the evolution of Treponema pallidum subsp. pallidum, the Syphilis Spirochete. mBio 9:e01006-18. 10.1128/mBio.01006-18 PubMed DOI PMC

Letunic I., Bork P. (2007). Interactive tree of life (iTOL): an online tool for phylogenetic tree display and annotation. Bioinformatics 23 127–128. 10.1093/bioinformatics/btl529 PubMed DOI

Li H. (2014). Toward better understanding of artifacts in variant calling from high-coverage samples. Bioinformatics 30 2843–2851. 10.1093/bioinformatics/btu356 PubMed DOI PMC

Li H., Handsaker B., Wysoker A., Fennell T., Ruan J., Homer N., et al. (2009). The sequence alignment/map format and SAMtools. Bioinformatics 25 2078–2079. 10.1093/bioinformatics/btp352 PubMed DOI PMC

Lomize M. A., Pogozheva I. D., Joo H., Mosberg H. I., Lomize A. L. (2012). OPM database and PPM web server: resources for positioning of proteins in membranes. Nucleic Acids Res. 40 D370–D376. 10.1093/nar/gkr703 PubMed DOI PMC

Marks M., Fookes M., Wagner J., Butcher R., Ghinai R., Sokana O., et al. (2018). Diagnostics for yaws eradication: insights from direct next-generation sequencing of cutaneous strains of Treponema pallidum. Clin. Infect. Dis. 66 818–824. 10.1093/cid/cix892 PubMed DOI PMC

Martin M. (2011). Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet.J. 17:10 10.14806/ej.17.1.200 DOI

Matĕjková P., Strouhal M., Šmajs D., Norris S. J., Palzkill T., Petrosino J. F., et al. (2008). Complete genome sequence of Treponema pallidum ssp. pallidum strain SS14 determined with oligonucleotide arrays. BMC Microbiol. 8:76. 10.1186/1471-2180-8-76 PubMed DOI PMC

McKenna A., Hanna M., Banks E., Sivachenko A., Cibulskis K., Kernytsky A., et al. (2010). The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20 1297–1303. 10.1101/gr.107524.110 PubMed DOI PMC

Mikalová L., Grillová L., Osbak K., Strouhal M., Kenyon C., Crucitti T., et al. (2017a). Molecular typing of syphilis-causing strains among human immunodeficiency virus-positive patients in antwerp, Belgium. Sex Transm. Dis. 44 376–379. 10.1097/OLQ.0000000000000600 PubMed DOI

Mikalová L., Strouhal M., Oppelt J., Grange P. A., Janier M., Benhaddou N., et al. (2017b). Human Treponema pallidum 11q/j isolate belongs to subsp. Endemicum but contains two loci with a sequence in TP0548 and TP0488 similar to subsp. pertenue and subsp. pallidum, respectively. PLoS Negl. Trop. Dis. 11:e0005434. 10.1371/journal.pntd.0005434 PubMed DOI PMC

Nechvátal L., Pětrošová H., Grillová L., Pospíšilová P., Mikalová L., Strnadel R., et al. (2014). Syphilis-causing strains belong to separate SS14-like or Nichols-like groups as defined by multilocus analysis of 19 Treponema pallidum strains. Int. J. Med. Microbiol. 304 645–653. 10.1016/j.ijmm.2014.04.007 PubMed DOI

Newman L., Rowley J., Vander Hoorn S., Wijesooriya N. S., Unemo M., Low N., et al. (2012). Global estimates of the prevalence and incidence of four curable sexually transmitted infections in based on systematic review and global reporting. PLoS One 10:e0143304. 10.1371/journal.pone.0143304 PubMed DOI PMC

Peeling R. W., Mabey D., Kamb M. L., Chen X.-S., Radolf J. D., Benzaken A. S. (2017). Syphilis. Nat. Rev. Dis. Primers. 3:17073. 10.1038/nrdp.2017.73 PubMed DOI PMC

Pětrošová H., Pospíšilová P., Strouhal M., Čejková D., Zobaníková M., Mikalová L., et al. (2013). Resequencing of Treponema pallidum ssp. pallidum strains Nichols and SS14: correction of sequencing errors resulted in increased separation of syphilis treponeme subclusters. PLoS One 8:e74319. 10.1371/journal.pone.0074319 PubMed DOI PMC

Pětrošová H., Zobaníková M., Čejková D., Mikalová L., Pospíšilová P., Strouhal M., et al. (2012). Whole genome sequence of Treponema pallidum ssp. pallidum, strain Mexico A, suggests recombination between yaws and syphilis strains. PLoS Negl. Trop. Dis. 6:e1832. 10.1371/journal.pntd.0001832 PubMed DOI PMC

Pinto M., Borges V., Antelo M., Pinheiro M., Nunes A., Azevedo J., et al. (2016). Genome-scale analysis of the non-cultivable Treponema pallidum reveals extensive within-patient genetic variation. Nat. Microbiol. 2:16190. 10.1038/nmicrobiol.2016.190 PubMed DOI

Pospíšilová P., Grange P. A., Grillová L., Mikalová L., Martinet P., Janier M., et al. (2018). Multi-locus sequence typing of Treponema pallidum subsp. Pallidum present in clinical samples from France: infecting treponemes are genetically diverse and belong to 18 allelic profiles. PLoS One 13:e0201068. 10.1371/journal.pone.0201068 PubMed DOI PMC

Quinlan A. R., Hall I. M. (2010). BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26 841–842. 10.1093/bioinformatics/btq033 PubMed DOI PMC

Radolf J. D., Deka R. K., Anand A., Šmajs D., Norgard M. V., Yang X. F. (2016). Treponema pallidum, the syphilis spirochete: making a living as a stealth pathogen. Nat. Rev. Microbiol. 14 744–759. 10.1038/nrmicro.2016.141 PubMed DOI PMC

Randall A., Cheng J., Sweredoski M., Baldi P. (2008). TMBpro: secondary structure, beta-contact and tertiary structure prediction of transmembrane beta-barrel proteins. Bioinformatics 24 513–520. 10.1093/bioinformatics/btm548 PubMed DOI

Remmert M., Biegert A., Hauser A., Söding J. (2011). HHblits: lightning-fast iterative protein sequence searching by HMM-HMM alignment. Nat. Methods 9 173–175. 10.1038/nmeth.1818 PubMed DOI

Šmajs D., Mikalova L., Strouhal M., Grillová L. (2016). Why are there two genetically distinct syphilis-causing strains? Forum Immunopathol. Dis. Ther. 7 181–190. 10.1615/forumimmundisther.2017020184 DOI

Šmajs D., Strouhal M., Knauf S. (2018). Genetics of human and animal uncultivable treponemal pathogens. Infect. Genet. Evol. 61 92–107. 10.1016/j.meegid.2018.03.015 PubMed DOI

Stamm L. V., Greene S. R., Barnes N. Y., Bergen H. L., Hardham J. M. (1997). Identification and characterization of a Treponema pallidum subsp. Pallidum gene encoding a DNA adenine methyltransferase. FEMS Microbiol. Lett. 155 115–119. 10.1016/s0378-1097(97)00375-3 PubMed DOI

Štaudová B., Strouhal M., Zobaníková M., Čejková D., Fulton L. L., Chen L., et al. (2014). Whole genome sequence of the Treponema pallidum subsp. Endemicum strain BosniaA: the genome is related to yaws treponemes but contains few loci similar to syphilis treponemes. PLoS Negl. Trop. Dis. 8:e3261. 10.1371/journal.pntd.0003261 PubMed DOI PMC

Stolte I. G., Dukers N. H., de Wit J. B., Fennema J. S., Coutinho R. A. (2001). Increase in sexually transmitted infections among homosexual men in Amsterdam in relation to HAART. Sex Transm. Infect. 77 184–186. 10.1136/sti.77.3.184 PubMed DOI PMC

Strouhal M., Mikalová L., Haviernik J., Knauf S., Bruisten S., Noordhoek G. T., et al. (2018). Complete genome sequences of two strains of Treponema pallidum subsp. Pertenue from Indonesia: modular structure of several treponemal genes. PLoS Negl. Trop. Dis. 12:e0006867. 10.1371/journal.pntd.0006867 PubMed DOI PMC

Strouhal M., Mikalová L., Havlíčková P., Tenti P., Čejková D., Rychlík I., et al. (2017). Complete genome sequences of two strains of Treponema pallidum subsp. Pertenue from Ghana, Africa: identical genome sequences in samples isolated more than 7 years apart. PLoS Negl. Trop. Dis. 11:e0005894. 10.1371/journal.pntd.0005894 PubMed DOI PMC

Tamura K., Peterson D., Peterson N., Stecher G., Nei M., Kumar S. (2011). MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol. Biol. Evol. 28 2731–2739. 10.1093/molbev/msr121 PubMed DOI PMC

Tong M.-L., Zhao Q., Liu L.-L., Zhu X.-Z., Gao K., Zhang H.-L., et al. (2017). Whole genome sequence of the Treponema pallidum subsp. Pallidum strain amoy: an asian isolate highly similar to SS14. PLoS One 12:e0182768. 10.1371/journal.pone.0182768 PubMed DOI PMC

Turner T. B., Hollander D. H. (1957). Biology of the treponematoses based on studies carried out at the international treponematosis Laboratory Center of the Johns Hopkins University under the auspices of the World Health Organization. Monogr. Ser. World Health Organ. 35 3–266. PubMed

Waterhouse A., Bertoni M., Bienert S., Studer G., Tauriello G., Gumienny R., et al. (2018). SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res. 46 W296–W303. 10.1093/nar/gky427 PubMed DOI PMC

Weinstock G. M., Smajs D., Hardham J., Norris S. J. (2000). From microbial genome sequence to applications. Res. Microbiol. 151 151–158. 10.1016/s0923-2508(00)00115-7 PubMed DOI

Woznicová V., Smajs D., Wechsler D., Matĕjková P., Flasarová M. (2007). Detection of Treponema pallidum subsp. pallidum from skin lesions, serum, and cerebrospinal fluid in an infant with congenital syphilis after clindamycin treatment of the mother during pregnancy. J. Clin. Microbiol. 45 659–661. 10.1128/jcm.02209-06 PubMed DOI PMC

Zobaníková M., Mikolka P., Čejková D., Pospíšilová P., Chen L., Strouhal M., et al. (2012). Complete genome sequence of Treponema pallidum strain DAL-1. Stand. Genomic Sci. 7 12–21. 10.4056/sigs.2615838 PubMed DOI PMC

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