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Updated: Oct 1, 2025
Forward Genetic Approaches in Chlamydia trachomatis
Published on: October 23, 2013
Whole-genome sequencing of Chlamydia trachomatis isolates from persistently infected patients
Rachel Pitt1, Ronan Doyle2, Mette Theilgaard Christiansen2
1National Infection Service, Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI), 372064Public Health England, London, UK.
Background:
Current understanding of the causes of treatment failure in Chlamydia trachomatis is poor and antimicrobial susceptibility data are lacking. We used genome sequencing to seek evidence of antimicrobial resistance in isolates sourced from patients who were persistently infected.
Methods:
Genomic DNA was extracted from C. trachomatis isolates cultured in McCoy cell monolayers. Sequencing libraries were prepared using the SureSelectXT Illumina paired-end protocol. Paired reads were mapped against a reference genome and single nucleotide variants (SNVs) were identified.
Results:
Seven isolates from persistently infected patients and five isolates from successfully treated patients were sequenced. No previously reported SNVs associated with antimicrobial resistance were found. A unique SNV was identified in the gyrA gene of one treatment failure isolate but was located outside of the quinolone resistance determining region; this SNV has been previously reported in other members of the Chlamydiaceae family.
Conclusion:
No genomic evidence was found to explain the differences in clinical outcome for our two groups of patients. A mutation unrelated to antimicrobial susceptibility was found in an isolate from a persistently infected patient. The cause of these persistent infections with C. trachomatis remains unclear.
Insights
Genomic analysis of Chlamydia trachomatis isolates revealed no antimicrobial resistance mutations explaining treatment failure. The causes of persistent C. trachomatis infections remain unclear, necessitating further research into treatment outcomes.
Area of Science:
- Microbiology
- Genomics
- Infectious Diseases
Background:
- Treatment failure in Chlamydia trachomatis infections is poorly understood.
- Antimicrobial susceptibility data for C. trachomatis are limited.
- Persistent C. trachomatis infections present a clinical challenge.
Purpose of the Study:
- To investigate genomic factors, specifically antimicrobial resistance, associated with treatment failure in Chlamydia trachomatis.
- To compare the genomes of C. trachomatis isolates from persistently infected patients with those from successfully treated patients.
Main Methods:
- Whole-genome sequencing was performed on C. trachomatis isolates.
- DNA was extracted from isolates cultured in McCoy cell monolayers.
- Single nucleotide variants (SNVs) were identified by mapping paired reads to a reference genome.
Main Results:
- No previously identified SNVs linked to antimicrobial resistance were detected in any isolates.
- A unique SNV in the gyrA gene was found in one treatment failure isolate, but it was outside the quinolone resistance-determining region and previously reported in other Chlamydiaceae.
- No genomic differences explained the varied clinical outcomes between the two patient groups.
Conclusions:
- Genomic sequencing did not reveal evidence of antimicrobial resistance contributing to C. trachomatis treatment failure in this cohort.
- A non-antimicrobial resistance mutation was identified in an isolate from a persistently infected patient.
- The underlying causes of persistent Chlamydia trachomatis infections require further investigation.
