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.

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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