Ceftriaxone resistance of T. pallidum introduced by natural in vitro mutagenesis

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F24%3A00138218" target="_blank" >RIV/00216224:14110/24:00138218 - isvavai.cz</a>

Result on the web

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DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Ceftriaxone resistance of T. pallidum introduced by natural in vitro mutagenesis

Original language description

The incidence of syphilis, caused by Treponema pallidum subsp. pallidum (TPA), remains high despite the available causative antibiotic therapy. The syphilis treatment was for many years considered straightforward due to the universal susceptibility of TPA to penicillin antibiotics 1 . We identified mutations A1873G and G2122A in the TP0705 gene in a clinical TPA isolate obtained from ceftriaxone treatment failure case. The A1873G mutation was successfully introduced into 2 laboratory TPA strains, which resulted in partial resistance to ceftriaxone and penicillin G in vitro 2 . Analysis of available sequence data revealed that the majority of contemporary TPA SS14 SS14-like strains 3 harbor this mutation and thus are partially resistant to ceftriaxone and penicillin G representing potential risk of TPA strains accumulating additional mutations leading to increased degree of ββ-lactam antibiotics resistance. New strategies in the syphilis control are thus needed 3 , therefore, extensive studies towards development of a multiplex syphilis vaccine are under way. The critical step of reliability of future vaccine 4 is the identification of suitable protein candidates along with the determination of antigenic diversity of these targets within TPA strains circulating in the human population. We analyzed TPA outer membrane determinants in 21 clinical samples preselected based on different MLST profile (Fig. 1) and revealed evolutionary processes consistent with adaptive evolution that in many bacterial pathogens operate in protein determinants involved in the host host-pathogen interactions. Our findings underscore the importance of analyzing TPA clinical samples isolated from diverse geographical regions in order to understand TPA outer membrane protein (OMP) variability worldwide. In addition to OMP variability, we tested potential differences in TPA physiology in vitro and revealed differences in generation times of individual TPA strains. Growth rates during in vitro coco-cultivation experiments of seven Treponema pallidum subsp. pallidum (TPA) strains including DAL DAL-1, Madras, Mexico A, Haiti B, SS14, Grady and Philadelphia 1 were assesed. During three week week-long co co-cultivation of 21 possible binary combinations (7×6/2), some TPA strains grew significantly faster compared to other strains. These differences among TPA strains might be responsible for variability of syphilis symptomatology observed in previous decades and centuries.

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

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OECD FORD branch

10607 - Virology

Project

<a href="/en/project/LX22NPO5103" target="_blank" >LX22NPO5103: National Institute of Virology and Bacteriology</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů