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We surveyed mutations and substitutions linked to putative azithromycin resistance across 1,349 high-quality\n                      <jats:italic toggle=\"yes\">C. trachomatis<\/jats:italic>\n                      genomes. Mutations in the\n                      <jats:italic toggle=\"yes\">rpl<\/jats:italic>\n                      V gene encoding three non-synonymous substitutions, compared with the canonical\n                      <jats:italic toggle=\"yes\">C. trachomatis<\/jats:italic>\n                      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\n                      <jats:italic toggle=\"yes\">23S<\/jats:italic>\n                      rRNA or\n                      <jats:italic toggle=\"yes\">rpl<\/jats:italic>\n                      D genes. This large-scale genomic surveillance provides critical insights into the evolutionary trends of putative azithromycin resistance in\n                      <jats:italic toggle=\"yes\">C. trachomatis<\/jats:italic>\n                      and underscores the importance of integrating genomic monitoring with phenotypic susceptibility testing to accurately assess and manage antimicrobial resistance.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01708-25","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T13:00:36Z","timestamp":1769432436000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Putative azithromycin resistance mutations in\n                    <i>Chlamydia trachomatis<\/i>\n                    are globally distributed but arose before azithromycin was discovered"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3065-4377","authenticated-orcid":true,"given":"Parul","family":"Sharma","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03czfpz43","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine","place":["Atlanta, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4490-1746","authenticated-orcid":true,"given":"Deborah","family":"Dean","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Global Health, Departments of Medicine and Pediatrics, University of California San Francisco School of Medicine","place":["San Francisco, USA"]},{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Bioengineering, Joint Program, University of California San Francisco and University of California Berkeley","place":["San Francisco, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8966-9680","authenticated-orcid":true,"given":"Timothy D.","family":"Read","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03czfpz43","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine","place":["Atlanta, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","first-page":"678","volume-title":"Duane\u2019s foundations of clinical ophthalmology","author":"Dean D","year":"2010","unstructured":"Dean D. 2010. Chapter 77, Pathogenesis of chlamydial ocular infections, p 678\u2013702. In TasmanW, JaegerEA (ed), Duane\u2019s foundations of clinical ophthalmology. Vol. 2. Lippincott Williams & Wilkins, Philadelphia, PA."},{"key":"e_1_3_3_3_2","unstructured":"World Health Organization. Chlamydia. Available from: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/chlamydia. Retrieved 12 Sep 2025."},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab153"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/24.3.363"},{"key":"e_1_3_3_6_2","volume-title":"Executive summaryWHO guideline on mass drug administration of azithromycin to children under five years of age to promote child survival","author":"World Health Organization","year":"2020","unstructured":"World Health Organization. 2020. Executive summary. WHO guideline on mass drug administration of azithromycin to children under five years of age to promote child survival. 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