title: 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.affiliation: Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, Montana, USA.
authors.forename: Harlan D
authors.initials: HD
authors.lastname: Caldwell
authors.forename: Heidi
authors.initials: H
authors.lastname: Wood
authors.forename: Debbie
authors.initials: D
authors.lastname: Crane
authors.forename: Robin
authors.initials: R
authors.lastname: Bailey
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jones
authors.forename: David
authors.initials: D
authors.lastname: Mabey
authors.forename: Ian
authors.initials: I
authors.lastname: Maclean
authors.forename: Zeena
authors.initials: Z
authors.lastname: Mohammed
authors.forename: Rosanna
authors.initials: R
authors.lastname: Peeling
authors.forename: Christine
authors.initials: C
authors.lastname: Roshick
authors.forename: Julius
authors.initials: J
authors.lastname: Schachter
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Solomon
authors.forename: Walter E
authors.initials: WE
authors.lastname: Stamm
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Suchland
authors.forename: Lacey
authors.initials: L
authors.lastname: Taylor
authors.forename: Sheila K
authors.initials: SK
authors.lastname: West
authors.forename: Tom C
authors.initials: TC
authors.lastname: Quinn
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Belland
authors.forename: Grant
authors.initials: G
authors.lastname: McClarty
mesh_terms: D000942:Antigens, Bacterial / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001483:Base Sequence; D015153:Blotting, Western; D002454:Cell Differentiation; D002692:Chlamydia trachomatis / Q000201:enzymology* / Q000235:genetics; D005123:Eye / Q000382:microbiology*; D005260:Female; D005836:Genitalia, Female / Q000382:microbiology*; D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity; D014367:Tryptophan Synthase / Q000235:genetics*
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D007211:Indoles; D008565:Membrane Proteins; D007371:Interferon-gamma; D014367:Tryptophan Synthase