Clinical Persistence of Chlamydia Trachomatis Sexually Transmitted Strains Involves Novel Mutations in the Functional Αββα Tetramer of the Tryptophan Synthase Operon

Chlamydia trachomatis(Ct) is the most common sexually transmitted bacterium with more than 131 million cases occurring annually worldwide.Ctinfections are often asymptomatic, persisting for many years despite treatment.In vitrorecovery from persistence occurs when indole is utilized by the organism’s tryptophan synthase to synthesize tryptophan, an essential amino acid for replication. Ocular but not urogenitalCtstrains contain mutations in the synthase that abrogate tryptophan synthesis. Here, we discovered that the genomes of serial isolates from a woman with recurrent, treatedCtSTIs over many years were identical with a novel synthase mutation. This likely allowed long-termin vivopersistence where active infection resumed only when tryptophan became available. Our findings indicate an emerging adaptive host-pathogen evolutionary strategy for survival in the urogenital tract that will prompt the field to further explore chlamydial persistence, evaluate the genetics of mutantCtstrains and fitness within the host, and their implications for disease pathogenesis.