BACKGROUND: For many years, syphilis treatment was considered straightforward due to the universal susceptibility of Treponema pallidum subsp. pallidum (TPA) to penicillin antibiotics. METHODS: Penicillin-binding protein genes from a ceftriaxone treatment failure T. pallidum isolate were assessed, and the introduction of identified mutations into two laboratory strains via natural competence was aimed for, followed by in vitro analysis of antibiotic susceptibility of the recombinants. RESULTS: TPA from the ceftriaxone treatment failure case contained A1873G and G2122A mutations in the TP0705 gene. Introduction of the A1873G mutation into laboratory strains DAL-1 and SS14 resulted in partial resistance to ceftriaxone and penicillin G in vitro. Furthermore, in silico analyses revealed that the majority of contemporary TPA SS14-like strains harbors this mutation and are thus partially resistant to ceftriaxone and penicillin G. CONCLUSIONS: This finding indicates that TPA strains accumulate mutations that increase their resistance to β-lactam antibiotics. Alternative approaches for controlling syphilis will be needed, including the development of the syphilis vaccine.

Penicillin antibiotics have been used to treat syphilis since the 1950s. Resistance to antibiotics is a growing concern. We investigated cases where antibiotics had failed to treat infection and found two mutations in a specific gene that could be responsible. Introduction of one of these mutations into two laboratory T. pallidum strains (the bacteria that cause syphilis) resulted in partial resistance to both ceftriaxone and penicillin antibiotics. Moreover, analysis of existing data revealed the presence of this mutation in numerous circulating T. pallidum strains, suggesting widespread partial resistance may already exist and increasing concerns about the future emergence of fully resistant syphilis strains.

Department of Biology Faculty of Medicine Masaryk University Brno Czech Republic

Department of Children's Infectious Disease Faculty of Medicine and University Hospital Masaryk University Brno Czech Republic

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