Polymorphisms in Chlamydia trachomatis tryptophan synthase genes differentiate between genital and ocular isolates


Caldwell, HD; Wood, H; Crane, D; Bailey, R; Jones, RB; Mabey, D; MacLean, I; Mohammed, Z; Peeling, R; Roshick, C; Schachter, J; Solomon, AW; Stamm, WE; Suchland, RJ; Taylor, L; West, SK; Quinn, TC; Belland, RJ; McClarty, G; (2003) Polymorphisms in Chlamydia trachomatis tryptophan synthase genes differentiate between genital and ocular isolates. The Journal of clinical investigation, 111 (11). pp. 1757-1769. ISSN 0021-9738 DOI: 10.1172/JCI17993

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Abstract

We previously reported that laboratory reference strains of Chlamydia trachomatis differing in infection organotropism correlated with inactivating mutations in the pathogen's tryptophan synthase (trpBA) genes. Here, we have applied functional genomics to extend this work and find that the paradigm established for reference serovars also applies to clinical isolates - specifically, all ocular trachoma isolates tested have inactivating mutations in the synthase, whereas all genital isolates encode a functional enzyme. Moreover, functional enzyme activity was directly correlated to IFN-gamma resistance through an indole rescue mechanism. Hence, a strong selective pressure exists for genital strains to maintain a functional synthase capable of using indole for tryptophan biosynthesis. The fact that ocular serovars (serovar B) isolated from the genital tract were found to possess a functional synthase provided further persuasive evidence of this association. These results argue that there is an important host-parasite relationship between chlamydial genital strains and the human host that determines organotropism of infection and the pathophysiology of disease. We speculate that this relationship involves the production of indole by components of the vaginal microbial flora, allowing chlamydiae to escape IFN-gamma-mediated eradication and thus establish persistent infection.

Item Type: Article
Keywords: outer-membrane protein, pelvic inflammatory disease, bacterial, vaginosis, interferon-gamma, cell-culture, indoleamine 2, 3-, dioxygenase, toxoplasma-gondii, host-cells, infections, pathogenesis, Antigens, Bacterial, metabolism, Bacterial Outer Membrane Proteins, metabolism, Base Sequence, Blotting, Western, Cell Differentiation, Chlamydia trachomatis, enzymology, genetics, Eye, microbiology, Female, Genitalia, Female, microbiology, Hela Cells, Human, Indoles, pharmacology, Interferon Type II, metabolism, Membrane Proteins, metabolism, Molecular Sequence Data, Mutation, Polymerase Chain Reaction, Polymorphism (Genetics), Reverse Transcriptase Polymerase Chain Reaction, Species Specificity, Support, Non-U.S. Gov't, Tryptophan Synthase, genetics
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
Research Centre: Malaria Centre
PubMed ID: 12782678
Web of Science ID: 183313400019
URI: http://researchonline.lshtm.ac.uk/id/eprint/16082

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