Resistance to ceftriaxone and penicillin G among contemporary syphilis strains confirmed by natural in vitro mutagenesis

Abstract 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 asse...

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Main Authors: Petra Pospíšilová, Juraj Bosák, Matěj Hrala, Lenka Krbková, Eliška Vrbová, David Šmajs
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Communications Medicine
Online Access:https://doi.org/10.1038/s43856-025-00948-x
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author Petra Pospíšilová
Juraj Bosák
Matěj Hrala
Lenka Krbková
Eliška Vrbová
David Šmajs
author_facet Petra Pospíšilová
Juraj Bosák
Matěj Hrala
Lenka Krbková
Eliška Vrbová
David Šmajs
author_sort Petra Pospíšilová
collection DOAJ
description Abstract 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.
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publisher Nature Portfolio
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spelling doaj-art-d1f7e37aae6e4e2a96a9c1d7bdb7a8982025-08-20T02:06:36ZengNature PortfolioCommunications Medicine2730-664X2025-06-01511710.1038/s43856-025-00948-xResistance to ceftriaxone and penicillin G among contemporary syphilis strains confirmed by natural in vitro mutagenesisPetra Pospíšilová0Juraj Bosák1Matěj Hrala2Lenka Krbková3Eliška Vrbová4David Šmajs5Department of Biology, Faculty of Medicine, Masaryk UniversityDepartment of Biology, Faculty of Medicine, Masaryk UniversityDepartment of Biology, Faculty of Medicine, Masaryk UniversityDepartment of Children’s Infectious Disease, Faculty of Medicine and University Hospital, Masaryk UniversityDepartment of Biology, Faculty of Medicine, Masaryk UniversityDepartment of Biology, Faculty of Medicine, Masaryk UniversityAbstract 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.https://doi.org/10.1038/s43856-025-00948-x
spellingShingle Petra Pospíšilová
Juraj Bosák
Matěj Hrala
Lenka Krbková
Eliška Vrbová
David Šmajs
Resistance to ceftriaxone and penicillin G among contemporary syphilis strains confirmed by natural in vitro mutagenesis
Communications Medicine
title Resistance to ceftriaxone and penicillin G among contemporary syphilis strains confirmed by natural in vitro mutagenesis
title_full Resistance to ceftriaxone and penicillin G among contemporary syphilis strains confirmed by natural in vitro mutagenesis
title_fullStr Resistance to ceftriaxone and penicillin G among contemporary syphilis strains confirmed by natural in vitro mutagenesis
title_full_unstemmed Resistance to ceftriaxone and penicillin G among contemporary syphilis strains confirmed by natural in vitro mutagenesis
title_short Resistance to ceftriaxone and penicillin G among contemporary syphilis strains confirmed by natural in vitro mutagenesis
title_sort resistance to ceftriaxone and penicillin g among contemporary syphilis strains confirmed by natural in vitro mutagenesis
url https://doi.org/10.1038/s43856-025-00948-x
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