Manoharan-Basil, S.; Gestels, Z.; Abdellati, S.; De Baetselier, I.; Vanbaelen, T.; Kenyon, C. Tetracycline Resistance Genes in Treponema spp.- an Analysis of 4355 Spirochaetales Genomes. Preprints2024, 2024030563. https://doi.org/10.20944/preprints202403.0563.v1
APA Style
Manoharan-Basil, S., Gestels, Z., Abdellati, S., De Baetselier, I., Vanbaelen, T., & Kenyon, C. (2024). Tetracycline Resistance Genes in <em>Treponema </em>spp.- an Analysis of 4355 Spirochaetales Genomes<strong> </strong>. Preprints. https://doi.org/10.20944/preprints202403.0563.v1
Chicago/Turabian Style
Manoharan-Basil, S., Thibaut Vanbaelen and Chris Kenyon. 2024 "Tetracycline Resistance Genes in <em>Treponema </em>spp.- an Analysis of 4355 Spirochaetales Genomes<strong> </strong>" Preprints. https://doi.org/10.20944/preprints202403.0563.v1
Abstract
Background: The resurgence of syphilis, primarily in MSM populations, has necessitated novel prophylactic strategies, such as the use of doxycycline post-exposure prophylaxis (doxy-PEP). However, the potential for increased doxycycline use to select for tetracycline resistance represents significant challenges in managing this sexually transmitted infection. This study aims to identify chromosomal mutations associated with tetracycline resistance in Spirochaetales to inform treatment strategies and surveillance measures.Methods: Whole genome sequences (WGS) from the Spirochaetales order, including 4,355 genomes, were analyzed for the presence of mutations in 16S rRNA and non-synonymous mutations in the rpsC and rpsJ genes. The study utilized WGS from GenBank® and sequence data from the PubMLST Treponema pallidum isolate collection. Genetic resistance to tetracycline was detected using a combination of BLASTN searches and gene-gene analysis. Results: A transition mutation TGA to TGG at positions 965-967 in the 16S rRNA gene was detected in 5.6% of Treponema spp. and 3.97% of Spirochaeta spp. genomes. The rpsJ gene exhibited a V57G amino acid substitution across a significant subset of Treponema spp. Notably, the V57K mutation was common in Spirochaeta spp. The rpsC gene had the H178Q mutation and was found to be present in the Spirochaetales bacterium.Conclusion: The identification of mutations associated with tetracycline resistance in Spirochaetales provides a foundation for the development of rapid molecular diagnostics and guides the clinical selection of antibiotics for syphilis treatment. This study underscores the complexity of antibiotic resistance mechanisms and the critical importance of surveillance in the era of antibiotic prophylaxis for STI management.
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