Genomic epidemiology ofTreponema pallidumand circulation of strains with diminishedtprKantigen variation capability in Seattle, 2021-2022

Abstract

AbstractBackgroundSyphilis incidence continues to increase dramatically in the United States and yet little is known aboutTreponema pallidum(TP) genomic epidemiology within American metropolitan areas.MethodsWe performed whole genome sequencing andtprKdeep sequencing of 28 TP-containing specimens collected mostly from remnant Aptima swabs from 24 individuals from Seattle Sexual Health Clinic during 2021-2022.ResultsAll 12 individuals infected with Nichols lineage strains were MSM, while a specific SS14 cluster (average 0.33 SNPs) included 1 MSW and five women. All TP strains sequenced were azithromycin resistant via 23S rRNA A2058G mutation. Identical TP genomic sequences were found in pharyngeal and rectal swab specimens taken from the same individuals concurrently.tprKsequences were less variable between patient-matched specimens and between epidemiologically-linked clusters. We detected a 528 bp deletion in thetprKdonor site locus, eliminating ninetprKdonor sites, in TP genomes of three individuals with secondary syphilis, associated with diminution of overalltprKsequence diversity.ConclusionsWe developed an end-to-end workflow for public health genomic surveillance of TP from remnant Aptima swab specimens. With its high rate of gene conversion,tprKsequencing may assist in linking cases beyond routine TP genome sequencing. TP strains with deletions intprKdonor sites currently circulate and are associated with diminished antigenic diversity of the TprK putative outer membrane protein.