title: Polymorphisms in the Chlamydia trachomatis cytotoxin locus associated with ocular and genital isolates.
abstract: Chlamydia trachomatis is a strict human pathogen producing infections that cause medically important chronic inflammatory diseases, such as blinding trachoma and tubal factor infertility. Isolates exist as serotypes that fall into distinct biologic and pathological groups corresponding to differences in infection tissue tropism and invasion properties. Paradoxically, genome sequencing of several diverse strains has revealed a remarkable level of genomic synteny, suggesting that minor genetic differences determine the pathogen host- and tissue-specific infection characteristics. To better understand the genetic basis of chlamydial pathobiologic diversity, we performed comparative DNA-DNA microarray genomic hybridizations with all 15 C. trachomatis serovariants. We found there are few major genetic differences among the 15 serovars. An exception was the cytotoxin locus located in the plasticity zone, a region that exhibited significant polymorphisms among serovars. We therefore sequenced this region from all 15 serovars. The cytotoxin gene was interrupted by extensive mutations and deletions among the different serovars; however, three basic open reading frame motifs were discovered that correlated with noninvasive oculotropic, urogenitotropic, and invasive serovars. Of interest, only noninvasive genitotropic serovars possessed an intact N-terminal portion of the putative toxin gene. This region contains the UDP-glucose binding domain and the glycosyltransferase domain required for enzymatic activity of the clostridial toxin homologs, suggesting a role in urogenital infection or pathogenesis.
authors.affiliation: College of Medicine, Department of Molecular Science, University of Tennessee, Memphis Health Science Center, 858 Madison Avenue, Memphis, TN 38163, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Carlson
authors.forename: Scott
authors.initials: S
authors.lastname: Hughes
authors.forename: Daniel
authors.initials: D
authors.lastname: Hogan
authors.forename: Gordon
authors.initials: G
authors.lastname: Cieplak
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Sturdevant
authors.forename: Grant
authors.initials: G
authors.lastname: McClarty
authors.forename: Harlan D
authors.initials: HD
authors.lastname: Caldwell
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Belland
mesh_terms: D001427:Bacterial Toxins / Q000235:genetics*; D001483:Base Sequence; D002692:Chlamydia trachomatis / Q000235:genetics* / Q000472:pathogenicity*; D002874:Chromosome Mapping; D003603:Cytotoxins / Q000235:genetics*; D005123:Eye / Q000382:microbiology; D005835:Genitalia / Q000382:microbiology; D016680:Genome, Bacterial; D006801:Humans; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D016366:Open Reading Frames; D011110:Polymorphism, Genetic
chemical_list: D001427:Bacterial Toxins; D003603:Cytotoxins