Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link

Disclaimer: Early release articles are not considered as final versions. Any changes will be reflected in the online version in the month the article is officially released.

Volume 32, Number 2—February 2026

Dispatch

Genomic Analysis of Doxycycline Resistance–Associated 16S rRNA Mutations in Treponema pallidum Subspecies pallidum

George S. Long, Mackenzie Neale, Thomas Braukmann, Vanessa Tran, Nishant Singh, Vanessa Allen, Muhammad Morshed, Jessica Minion, Paul Van Caeseele, Maud Vallée, Todd Hatchette, Samir N. Patel, Raymond S.W. Tsang, and Venkata R. DuvvuriComments to Author 
Author affiliation: Public Health Ontario, Toronto, Ontario, Canada (G.S. Long, T. Braukmann, V. Tran, N. Singh, V. Allen, S.N. Patel, V.R. Duvvuri); Public Health Agency of Canada, Winnipeg, Manitoba, Canada (M. Neale, R.S.W. Tsang); University of Toronto, Toronto (T. Braukmann, V. Tran, V. Allen, S.N. Patel, V.R. Duvvuri); Sinai Health and University Health Network, Toronto (V. Allen); British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada (M. Morshed); University of British Columbia, Vancouver (M. Morshed); Roy Romanow Provincial Laboratory, Regina, Saskatchewan, Canada (J. Minion); University of Saskatchewan, Regina (J. Minion); Cadham Provincial Laboratory, Winnipeg (P. Van Caeseele); University of Manitoba, Winnipeg (P. Van Caeseele); Laboratoire de Santé Publique du Québec, Sainte-Anne-de-Bellevue, Quebec, Canada (M. Vallée); Dalhousie University, Halifax, Nova Scotia, Canada (T. Hatchette); York University, Toronto (V.R. Duvvuri)

Main Article

Table 2

16S rRNA mutations related to tetracycline resistance in genomic analysis of doxycycline resistance-associated 16S rRNA mutations in Treponema pallidum subsp. pallidum*

Species Resistance mutations using E. coli (U00096.1) coordinates Species-specific coordinates Reference
Escherichia coli A964G, G1053A, C1054T, A1055G A966G, G1056A, C1057T, A1058G (8)
Cutibacterium acnes G1058C G1032C (7)
Helicobacter pylori A965G, A965G & A967C, A965G & G966T, A967C A930G, A930G & A932C, A930G & G931T, A932C (6)

*Ampersands in the resistance mutations column indicate multi-allele resistance variants.

Main Article

References
  1. Cato  K, Chuang  E, Connolly  KL, Deal  C, Hiltke  T. Summary of the National Institute of Allergy and Infectious Diseases workshop on alternative therapies to penicillin for the treatment of syphilis. Sex Transm Dis. 2025;52:20110. DOIPubMedGoogle Scholar
  2. Hazra  A, McNulty  MC, Pyra  M, Pagkas-Bather  J, Gutierrez  JI, Pickett  J, et al. Filling in the gaps: updates on doxycycline prophylaxis for bacterial sexually transmitted infections. Clin Infect Dis. 2024:ciae062. DOIGoogle Scholar
  3. Dai  T, Qu  R, Liu  J, Zhou  P, Wang  Q. Efficacy of doxycycline in the treatment of syphilis. Antimicrob Agents Chemother. 2016;61:e0109216. DOIPubMedGoogle Scholar
  4. Grossman  TH. Tetracycline antibiotics and resistance. Cold Spring Harb Perspect Med. 2016;6:a025387. DOIPubMedGoogle Scholar
  5. Dailidiene  D, Bertoli  MT, Miciuleviciene  J, Mukhopadhyay  AK, Dailide  G, Pascasio  MA, et al. Emergence of tetracycline resistance in Helicobacter pylori: multiple mutational changes in 16S ribosomal DNA and other genetic loci. Antimicrob Agents Chemother. 2002;46:39406. DOIPubMedGoogle Scholar
  6. Ross  JI, Eady  EA, Cove  JH, Cunliffe  WJ. 16S rRNA mutation associated with tetracycline resistance in a gram-positive bacterium. Antimicrob Agents Chemother. 1998;42:17025. DOIPubMedGoogle Scholar
  7. Yassin  A, Fredrick  K, Mankin  AS. Deleterious mutations in small subunit ribosomal RNA identify functional sites and potential targets for antibiotics. Proc Natl Acad Sci U S A. 2005;102:166205. DOIPubMedGoogle Scholar
  8. Stamm  LV. Global challenge of antibiotic-resistant Treponema pallidum. Antimicrob Agents Chemother. 2010;54:5839. DOIPubMedGoogle Scholar
  9. Lieberman  NAP, Lin  MJ, Xie  H, Shrestha  L, Nguyen  T, Huang  ML, et al. Treponema pallidum genome sequencing from six continents reveals variability in vaccine candidate genes and dominance of Nichols clade strains in Madagascar. PLoS Negl Trop Dis. 2021;15:e0010063.PubMedGoogle Scholar
  10. Tantalo  LC, Luetkemeyer  AF, Lieberman  NAP, Nunley  BE, Avendaño  C, Greninger  AL, et al. In vitro exposure of Treponema pallidum to subbactericidal doxycycline did not induce resistance: implications for doxycycline postexposure prophylaxis. J Infect Dis. 2025;231:72933. DOIPubMedGoogle Scholar
  11. Manoharan-Basil  SS, Gestels  Z, Abdellati  S, de Block  T, Vanbaelen  T, De Baetselier  I, et al. Putative mutations associated with tetracycline resistance detected in Treponema spp.: an analysis of 4,355 Spirochaetales genomes. Access Microbiol. 2025;7:000963.v4.
  12. Stamm  LV, Bergen  HL. A point mutation associated with bacterial macrolide resistance is present in both 23S rRNA genes of an erythromycin-resistant Treponema pallidum clinical isolate. Antimicrob Agents Chemother. 2000;44:8067. DOIPubMedGoogle Scholar
  13. Grillová  L, Bawa  T, Mikalová  L, Gayet-Ageron  A, Nieselt  K, Strouhal  M, et al. Molecular characterization of Treponema pallidum subsp. pallidum in Switzerland and France with a new multilocus sequence typing scheme. PLoS One. 2018;13:e0200773.PubMedGoogle Scholar
  14. Long  G, Singh  N, Patel  S, Braukmann  T, Tsang  RSW, Duvvuri  VR. Integrated genomic approaches improve Treponema pallidum phylogenetics and lineage classification. Can J Microbiol. 2025;71:111. DOIPubMedGoogle Scholar

Main Article

Page created: January 16, 2026
Page updated: February 09, 2026
Page reviewed: February 09, 2026
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external