Investigating_the_role_of_bacterial_genetic_variation_in_syphilis_disease_progression_using_whole_genome_sequencing. Investigating_the_role_of_bacterial_genetic_variation_in_syphilis_disease_progression_using_whole_genome_sequencing

The causative pathogen of the syphilis infection is Treponema pallidum subspecies pallidum (TPA), and the genome was first sequenced in 1998. However, most early genomes were sequenced after substantial passage in the rabbit model, and large scale sequencing directly from clinical patients has only become feasible in the last few years. To date, the majority of Treponema genomics studies have been performed on opportunistically collected patient samples, with limited clinical information and patient connectivity metadata. Syphilis is characterised by active diseases stages (primary, secondary, tertiary), separated by periods of latency that can span months to decades. The three disease stages are classically described as quite distinct clinical conditions, with different symptoms and sequelae. The TREPOLI study conducted in Amsterdam (Netherlands), has been prospectively following and collecting samples from MSM patients with an infectious syphilis infection (primary, secondary or early latent stage), including collecting multiple samples per patient at different body sites (primary ulcer, urine, peripheral blood, a pharyngeal swab and a throat swab). This collection presents an unusual opportunity to explore the genomics of syphilis disease progression within a high prevalence population. We hypothesise that progression from primary to secondary syphilis is associated with adaptive bacterial genomic changes. To address this question, we will use a paired case-control design, performing whole genome sequencing of TPA from patients with primary and secondary syphilis in the same community in order to determine if there is evidence of convergent evolution (e.g. through homoplasic variants) associated with disease progression. By including samples from different body sites in the study, we will also be able to assess whether there are particular variants associated with different ecological niches (i.e. body sites). Aims and Objectives: To investigate the genomic differences between T. pallidum causing primary and secondary syphilis. Sample Size: Up to 30 patients (14 primary, 14 secondary, 2 early latent), will be included, and we will sequence multiple samples per patient (up to 66 samples in total). This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/