How Chlamydia trachomatis conquered gut microbiome-derived antimicrobial compounds and found a new home in the eye

Different variants of the obligate intracellular bacterial pathogen Chlamydia trachomatis cause the diseases trachoma and chlamydia. The trachoma strains cause chronic infections of the conjunctival epithelium and an intense inflammatory response that can lead to corneal damage, and trachoma is the most common cause of infectious blindness. The Chlamydia strains preferentially infect columnar epithelial cells of the cervix or urethra, and Chlamydia is the most common bacterial sexually transmitted infection. Chlamydia strains often elicit no symptoms but sometimes ascend the reproductive tract where they can elicit chronic inflammation and severe consequences, including pelvic inflammatory disease. Despite their distinct tissue tropisms, the genomes of the trachoma and Chlamydia strains are nearly identical (1). Chlamydia genital tropism has been linked to tryptophan synthase (TS), an enzyme that synthesizes tryptophan from indole (Fig. 1) (2, 3). Expression of the α-subunit (TrpA) and β-subunit (TrpB) of the TS holoenzyme is tightly regulated by an apo-repressor (TrpR) (4⇓⇓–7). In the presence of the corepressor tryptophan, TrpR binds an operator sequence ( trpO ) and blocks trpBA transcription. Low tryptophan levels promote TrpR release from trpO and allow TS expression. Chlamydia strains likely use TS to circumvent immune-regulated tryptophan catabolism, mediated by the host enzyme indoleamine 2,3′ dioxygenase (IDO1) (2). In contrast, most trachoma isolates do not express a functional TS (2). A study in PNAS by Sherchand and Aiyar (8 … [↵][1]1To whom correspondence may be addressed. Email: nelsonde{at}indiana.edu. [1]: #xref-corresp-1-1