Genome-wide association studies of <i>C. trachomatis</i> identify novel tissue tropism-predicting loci and sequences that discriminate among major genome sequence clades

ABSTRACT Chlamydia trachomatis infections cause chronic and debilitating diseases of the eye and genital tract. Recent data suggest that infections are common at other tissue sites, including the lower intestinal tract of both men and women. Our previous work demonstrated tropism-predicting sequences in male rectal isolates, with modification in the PmpE sequence and predicted structure being highly correlated with male rectal infection. An expanded collection of strains from five different tissue sites was used to identify novel tropism-predicting markers for the different tissues. These data demonstrate that C. trachomatis strains colonizing the male rectum are unique with respect to all other tested sites. Additionally, ocular strains have a consistent set of genes that separate them from strains isolated from any other tissue. Novel polymorphisms predictive of ocular tropism include a single indel in mrcA and a region between pmpH and pmpI , including the hypothetical gene ct873 . These analyses also identified a novel urogenital clade, termed the variable-OmpA clade, in which strains carry a variety of ompA sequences in an otherwise shared genomic background. This clade is defined primarily by single-nucleotide polymorphisms (SNPs) within and adjacent to the highly variable plasticity zone. Collectively, this work explores the continuing evolution of C. trachomatis strains and clades in a genomic background that only engages in intraspecies horizontal gene transfer.