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Forward Genetic Approaches in Chlamydia trachomatis
Published on: October 23, 2013
Putative azithromycin resistance mutations in Chlamydia trachomatis are globally distributed but arose before
Parul Sharma1, Deborah Dean2,3, Timothy D Read1
1Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
Abstract:
Azithromycin is widely used to treat Chlamydia trachomatis infections, yet the extent of resistance to the drug across the species has not been addressed. We surveyed mutations and substitutions linked to putative azithromycin resistance across 1,349 high-quality C. trachomatis genomes. Mutations in the rplV gene encoding three non-synonymous substitutions, compared with the canonical C. trachomatis reference strain D//TW-3/Cx sequence, were found to be common but largely conserved within phylogenetic lineages causing prevalent urogenital and anorectal infections and lymphogranuloma venereum. However, no mutations were identified in the ocular lineage. Time-scaled phylogenetic analysis suggested that these mutations predate the clinical introduction of azithromycin. In contrast, no consistent resistance-associated patterns were observed in 23S rRNA or rplD genes. This large-scale genomic surveillance provides critical insights into the evolutionary trends of putative azithromycin resistance in C. trachomatis and underscores the importance of integrating genomic monitoring with phenotypic susceptibility testing to accurately assess and manage antimicrobial resistance.
Insights
Azithromycin resistance mutations in Chlamydia trachomatis are common in certain lineages but absent in ocular strains. These mutations appear to predate the drug's clinical use, highlighting the need for genomic surveillance.
Area of Science:
- Genomics
- Microbiology
- Antimicrobial Resistance
Background:
- Azithromycin is a key treatment for Chlamydia trachomatis.
- The prevalence and patterns of azithromycin resistance across C. trachomatis species are not well understood.
Purpose of the Study:
- To investigate mutations associated with azithromycin resistance in C. trachomatis using genomic data.
- To understand the evolutionary trends of resistance in different C. trachomatis lineages.
Main Methods:
- Analysis of 1,349 high-quality C. trachomatis genomes.
- Identification and comparison of mutations and substitutions linked to azithromycin resistance.
- Time-scaled phylogenetic analysis to date mutation emergence.
Main Results:
- Mutations in the rplV gene were common and lineage-specific, particularly in strains causing urogenital, anorectal, and lymphogranuloma venereum infections.
- No resistance-associated mutations were found in the ocular C. trachomatis lineage.
- Phylogenetic analysis indicated that identified rplV mutations likely predate azithromycin's clinical introduction.
- No consistent resistance patterns were observed in 23S rRNA or rplD genes.
Conclusions:
- Genomic surveillance reveals lineage-specific patterns of putative azithromycin resistance in C. trachomatis.
- The findings suggest that resistance mechanisms may have evolved prior to widespread azithromycin use.
- Integrating genomic data with susceptibility testing is crucial for managing antimicrobial resistance in C. trachomatis.
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