In Vitro Exposure of Treponema pallidum to Subbactericidal Doxycycline Did Not Induce Resistance: Implications for Doxycycline Postexposure Prophylaxis

J Infect Dis. 2025 Mar 17;231(3):729-733. doi: 10.1093/infdis/jiae381.

Abstract

Doxycycline postexposure prophylaxis (doxy-PEP) could significantly reduce syphilis incidence. However, the increase in intermittent doxycycline usage might select resistant Treponema pallidum strains. To assess whether resistance to doxycycline could be induced in this pathogen, we exposed the SS14 strain in vitro, both intermittently and continuously, to a subbactericidal doxycycline concentration that still exerts antibiotic pressure. During and after each exposure experiment, we assessed the doxycycline minimal inhibitory concentration in test and control treponemes and performed whole-genome sequencing, concluding that no resistance developed. This work suggests that doxycycline-resistant T. pallidum is not an immediate threat for doxy-PEP implementation.

Keywords: Treponema pallidum subsp. pallidum; doxycycline; in vitro propagation; resistance; syphilis.

MeSH terms

  • Anti-Bacterial Agents* / administration & dosage
  • Anti-Bacterial Agents* / pharmacology
  • Doxycycline* / administration & dosage
  • Doxycycline* / pharmacology
  • Drug Resistance, Bacterial*
  • Humans
  • Microbial Sensitivity Tests
  • Post-Exposure Prophylaxis* / methods
  • Syphilis* / microbiology
  • Syphilis* / prevention & control
  • Treponema pallidum* / drug effects
  • Treponema pallidum* / genetics
  • Whole Genome Sequencing

Substances

  • Doxycycline
  • Anti-Bacterial Agents