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

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.

• Authors: Harlan D Caldwell, Heidi Wood, Debbie Crane, Robin Bailey, Robert B Jones, David Mabey, Ian Maclean, Zeena Mohammed, Rosanna Peeling, Christine Roshick, Julius Schachter, Anthony W Solomon, Walter E Stamm, Robert J Suchland, Lacey Taylor, Sheila K West, Tom C Quinn, Robert J Belland, Grant McClarty
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 111 Issue 11 Pg. 1757-69 (Jun 2003) ISSN: 0021-9738 [Print] United States
• PMID: 12782678 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Bacterial
• Bacterial Outer Membrane Proteins
• Indoles
• Membrane Proteins
• Interferon-gamma
• Tryptophan Synthase

Topics

• 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
• Humans
• Indoles (pharmacology)
• Interferon-gamma (metabolism)
• Membrane Proteins (metabolism)
• Molecular Sequence Data
• Mutation
• Polymerase Chain Reaction
• Polymorphism, Genetic
• Reverse Transcriptase Polymerase Chain Reaction
• Species Specificity
• Tryptophan Synthase (genetics)