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Volume 32, Number 8—August 2026
Letter
Doxycycline Resistance and 16S rRNA Mutations in Treponema pallidum (Response)
Suggested citation for this article
In Response: On March 5, 2026, Drs. Lieberman and Beale contacted us concerning the identification of a heterozygous allele at position G966T (by E. coli reference numbering, G969T by T. pallidum reference numbering) of the 16S rRNA gene of Treponema pallidum subspecies pallidum (1). They surmised that our identification of the allele may have been caused by either genome misassemblies or contamination with sequences from other Trepomena species (2). In response to these reproducibility concerns, we undertook a separate analysis using an independent analytical process from our original work (1).
Our reanalysis focused on the sequencing libraries of Beale et al. (3–5) and applied a mapping-based approach, aligning reads to the 16S rRNA gene of the T. pallidum reference genome (NC_021490.2:231255–232803). That reanalysis concluded that the previously identified heterozygous allele was indeed the result of contamination. Accordingly, Table 4 and text associated with the heterozygous single-nucleotide polymorphism have been removed from the original article. In addition, an extra paragraph has been added to the Appendix detailing the additional analyses.
Of note, the overall findings of our study remain unaffected. We still report the sequencing and assembly of 15 T. pallidum subsp. pallidum genomes from Canada. This revision strengthens the clarity of our comparative genomics analysis and simplifies the identification of single-nucleotide polymorphisms related to putative doxycycline resistance and underscore the importance of accounting for the presence of two 16S rRNA gene copies in T. pallidum. This study continues to represent a vital step in establishing a genomic baseline for monitoring circulating T. pallidum subsp. pallidum lineages in Canada.
References
- Long GS, Neale M, Braukmann T, Tran V, Singh N, Allen V, et al. Genomic analysis of doxycycline resistance–associated 16S rRNA mutations in Treponema pallidum subspecies pallidum. Emerg Infect Dis. 2026;32:242–5. DOIPubMedGoogle Scholar
- Beale MA, Marks M, Luetkemeyer A, Celum C, Golden MR, Giacani L, et al. Doxycycline resistance and 16S rRNA mutations in Treponema pallidum. Emerg Infect Dis. 2026;32:XXX. DOIPubMedGoogle Scholar
- Beale MA, Marks M, Sahi SK, Tantalo LC, Nori AV, French P, et al. Genomic epidemiology of syphilis reveals independent emergence of macrolide resistance across multiple circulating lineages. Nat Commun. 2019;10:3255. DOIPubMedGoogle Scholar
- Beale MA, Marks M, Cole MJ, Lee MK, Pitt R, Ruis C, et al. Global phylogeny of Treponema pallidum lineages reveals recent expansion and spread of contemporary syphilis. Nat Microbiol. 2021;6:1549–60. DOIPubMedGoogle Scholar
- Beale MA, Thorn L, Cole MJ, Pitt R, Charles H, Ewens M, et al. Genomic epidemiology of syphilis in England: a population-based study. Lancet Microbe. 2023;4:e770–80. DOIPubMedGoogle Scholar
Suggested citation for this article: Long GS, Duvvuri VR. Doxycycline resistance and 16S rRNA mutations in Treponema pallidum (Response). Emerg Infect Dis. 2026 Aug [date cited]. https://doi.org/10.3201/eid3208.260943
Original Publication Date: July 16, 2026
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Table of Contents – Volume 32, Number 8—August 2026
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Please use the form below to submit correspondence to the authors or contact them at the following address:
Venkata R. Duvvuri, Public Health Ontario, 661 University Ave, Ste 1701, Toronto, ON M5G 1M1, Canada
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