In vitro rescue of genital strains of Chlamydia trachomatis from interferon-γ and tryptophan depletion with indole-positive, but not indole-negative Prevotella spp. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Ziklo, Noa; Huston, Wilhelmina; Taing, Kuong; Katouli, Mohammad; Timms, Peter
• Is Part Of: BMC microbiology. Volume 16:Issue 1(2016)
• Page Start: 1
• Page End: 10
• Publication Date: 2016-12
• Subjects: Tryptophan-synthase -- Interferon-γ -- Microbiota; Microbiology -- Periodicals; 579.05
• DOI: 10.1186/s12866-016-0903-4
• Languages: English
• ISSNs: 1471-2180

Abstract

Abstract Background The natural course of sexually transmitted infections caused byChlamydia trachomatis varies between individuals. In addition to parasite and host effects, the vaginal microbiota might play a key role in the outcome ofC. trachomatis infections. Interferon-gamma (IFN-γ), known for its anti-chlamydial properties, activates the expression of indoleamine 2, 3-dioxygenase (IDO1) in epithelial cells, an enzyme that catabolizes the amino acid L- tryptophan into N-formylkynurenine, depleting the host cell's pool of tryptophan. AlthoughC. trachomatis is a tryptophan auxotroph, urogenital strains (but not ocular strains) have been shown in vitro to have the ability to produce tryptophan from indole using the tryptophan synthase (trpBA ) gene. It has been suggested that indole producing bacteria from the vaginal microbiota could influence the outcome ofChlamydia infection. Results We used two in vitro models (treatment with IFN-γ or direct limitation of tryptophan), to study the effects of direct rescue by the addition of exogenous indole, or by the addition of culture supernatant from indole-positive versus indole-negativePrevotella strains, on the growth and infectivity ofC. trachomatis . We found that only supernatants from the indole-positive strains, P. intermedia andP. nigrescens, were able to rescue tryptophan-starvedC. trachomatis . In addition, we analyzed vaginal secretion samples to determine physiological indole concentrations. In spite of the complexity of vaginal secretions, we demonstrated that for some vaginal specimens with higher indole levels, there was a link to higher recovery of theChlamydia under tryptophan-starved conditions, lending preliminary support to the critical role of the IFN-γ-tryptophan-indole axis in vivo. Conclusions Our data provide evidence for the ability of both exogenous indole as well as supernatant from indole producing bacteria such asPrevotella, to rescue genitalC. trachomatis from tryptophan starvation. This adds weight to the hypothesis that the vaginal microbiota (particularly from women with lower levels of lactobacilli and higher levels of indole producing anaerobes) may be intrinsically linked to the outcome of chlamydial infections in some women.