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.

Center for Bioinformatics University of Tübingen Tübingen Germany

Department of Anthropology University of Zurich Zurich Switzerland

Department of Biology Masaryk University Brno Czech Republic

Department of Dermatology Triemlispital Zurich Switzerland

Department of Dermatology University Hospital Zurich Zurich Switzerland

Department of Fundamental Neuroscience University of Geneva Geneva Switzerland

Department of Infectious Diseases Centre Hospitalier Universitaire Vaudois Lausanne Switzerland

Division of Clinical Epidemiology University of Geneva Hospitals and Faculty of Medicine Geneva Switzerland

Faculty of Medicine University of Zurich Zurich Switzerland

Hospices civils de Lyon Lyon France

IMD Institut für medizinische and molekulare Diagnostik AG Zurich Switzerland

Institute for Evolutionary Biology and Environmental Studies University of Zurich Zurich Switzerland

Medical Biology Institute Alfred Fournier Paris France

Repsol Technology Center Madrid Spain

Unidad Mixta Infección y Salud Pública FISABIO Universidad de Valencia CIBER in Epidemiology and Public Health Valencia Spain

Zurich Institute of Forensic Medicine University of Zurich Zurich Switzerland

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Clinical and genomic diversity of Treponema pallidum subspecies pallidum to inform vaccine research: an international, molecular epidemiology study

Majority of Treponema pallidum ssp. pallidum MLST allelic profiles in the Czech Republic (2004-2022) belong to two SS14-like clusters

Treponema pallidum subsp. pallidum strains DAL-1 and Philadelphia 1 differ in generation times in vitro as well as during experimental rabbit infection

Low genetic diversity of Treponema pallidum ssp. pertenue (TPE) isolated from patients' ulcers in Namatanai District of Papua New Guinea: Local human population is infected by three TPE genotypes

High frequency of Nichols-like strains and increased levels of macrolide resistance in Treponema pallidum in clinical samples from Buenos Aires, Argentina

Whole genome sequences of Treponema pallidum subsp. endemicum isolated from Cuban patients: The non-clonal character of isolates suggests a persistent human infection rather than a single outbreak

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

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Penicillin Treatment Failure in Rabbit Syphilis Due to the Persistence of Treponemes (Treponema paraluisleporidarum Ecovar Cuniculus) in the Focus of Infection

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No bejel among Surinamese, Antillean and Dutch syphilis diagnosed patients in Amsterdam between 2006-2018 evidenced by multi-locus sequence typing of Treponema pallidum isolates

Strain diversity of Treponema pallidum subsp. pertenue suggests rare interspecies transmission in African nonhuman primates

Directly Sequenced Genomes of Contemporary Strains of Syphilis Reveal Recombination-Driven Diversity in Genes Encoding Predicted Surface-Exposed Antigens

Identification of positively selected genes in human pathogenic treponemes: Syphilis-, yaws-, and bejel-causing strains differ in sets of genes showing adaptive evolution

MLST typing of Treponema pallidum subsp. pallidum in the Czech Republic during 2004-2017: Clinical isolates belonged to 25 allelic profiles and harbored 8 novel allelic variants

A public database for the new MLST scheme for Treponema pallidum subsp. pallidum: surveillance and epidemiology of the causative agent of syphilis

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

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