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Polymorphisms in Chlamydia trachomatis tryptophan synthase genes differentiate between genital and ocular isolates.
Polymorphisms in Chlamydia trachomatis tryptophan synthase genes differentiate between genital and ocular isolates.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 2003 Jun; Vol. 111 (11), pp. 1757-69. - Publication Year :
- 2003
-
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.
- Subjects :
- Antigens, Bacterial metabolism
Bacterial Outer Membrane Proteins metabolism
Base Sequence
Blotting, Western
Cell Differentiation
Chlamydia trachomatis genetics
Female
HeLa Cells
Humans
Indoles pharmacology
Interferon-gamma metabolism
Membrane Proteins metabolism
Molecular Sequence Data
Mutation
Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Species Specificity
Chlamydia trachomatis enzymology
Eye microbiology
Genitalia, Female microbiology
Polymorphism, Genetic
Tryptophan Synthase genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9738
- Volume :
- 111
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 12782678
- Full Text :
- https://doi.org/10.1172/JCI17993