title: In vitro rescue of genital strains of Chlamydia trachomatis from interferon-γ and tryptophan depletion with indole-positive, but not indole-negative Prevotella spp.
abstract: BACKGROUND
  The natural course of sexually transmitted infections caused by Chlamydia trachomatis varies between individuals. In addition to parasite and host effects, the vaginal microbiota might play a key role in the outcome of C. 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. Although C. 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 of Chlamydia 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-negative Prevotella strains, on the growth and infectivity of C. trachomatis. We found that only supernatants from the indole-positive strains, P. intermedia and P. nigrescens, were able to rescue tryptophan-starved C. 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 the Chlamydia 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 as Prevotella, to rescue genital C. 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.
authors.affiliation: University of Sunshine Coast, 90 Sippy Downs Dr, Sippy Downs, Queensland, 4556, Australia. Noa.Ziklo@research.usc.edu.au.
authors.forename: Noa
authors.initials: N
authors.lastname: Ziklo
authors.affiliation: University of Technology Sydney, 745 Harris St, Ultimo, New South Wales, 2007, Australia.
authors.forename: Wilhelmina M
authors.initials: WM
authors.lastname: Huston
authors.affiliation: Sexual health and HIV Service, Clinic 87, Sunshine Coast, Queensland, Australia.
authors.forename: Kuong
authors.initials: K
authors.lastname: Taing
authors.affiliation: University of Sunshine Coast, 90 Sippy Downs Dr, Sippy Downs, Queensland, 4556, Australia.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Katouli
authors.affiliation: University of Sunshine Coast, 90 Sippy Downs Dr, Sippy Downs, Queensland, 4556, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Timms
mesh_terms: D002690:Chlamydia Infections / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D002692:Chlamydia trachomatis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004847:Epithelial Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D005260:Female; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D066298:In Vitro Techniques; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D007211:Indoles / Q000378:metabolism*; D007371:Interferon-gamma / Q000172:deficiency* / Q000276:immunology; D007737:Kynurenine / Q000031:analogs & derivatives / Q000378:metabolism; D064307:Microbiota; D018720:Prevotella / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014364:Tryptophan / Q000172:deficiency* / Q000276:immunology; D014367:Tryptophan Synthase / Q000235:genetics / Q000378:metabolism; D014623:Vaginal Diseases / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007211:Indoles; D012333:RNA, Messenger; C007772:N'-formylkynurenine; D007737:Kynurenine; D007371:Interferon-gamma; D014364:Tryptophan; D014367:Tryptophan Synthase
keywords: Interferon-γ; Microbiota; Tryptophan-synthase