TheompAGene inChlamydia trachomatisDiffers in Phylogeny and Rate of Evolution from Other Regions of the Genome

Abstract

Strains of Chlamydia trachomatis are classified into serovars based on nucleotide sequence differences in ompA, the gene that encodes the major outer membrane protein. Phylogenetic characterization of strains based on ompA, however, results in serovar groupings that are inconsistent with the distinguishing features of C. trachomatis pathobiology, e.g., tissue tropisms and disease presentation. We have compared nucleotide sequences at multiple sites distributed around the chlamydial genome from 18 strains representing 16 serovars; sampled regions included genes encoding housekeeping enzymes (totaling 2,073 bp), intergenic noncoding segments (1,612 bp), and a gene encoding a second outer membrane protein ( porB; 1,023 bp), with the ompA sequence (1,194 bp) used for reference. These comparative analyses revealed substantial variation in nucleotide substitution patterns among the sampled regions, with average pairwise sequence differences ranging from 0.15% for the housekeeping genes to 12.1% for ompA. Phylogenetic characterization of the sampled genomic sequences yielded a strongly supported tree that divides the strains into groupings consistent with C. trachomatis biology and which has a topology quite distinct from the ompA tree. This phylogenetic incongruity can be accounted for by recombination of the ompA gene between different genomic backgrounds. We found, however, no evidence of recombination within or between any of the sampled regions around the C. trachomatis genome apart from ompA. Parallel analysis of published sequence data on four members of the pmp gene family are consistent with the phylogenetic analyses reported here.

Phylogenetic Analysis ofChlamydia trachomatisTarp and Correlation with Clinical Phenotype

“…In both clusters, the non-C. trachomatis reference strains appeared to group separately in an outgroup distinct from the C. trachomatis reference strains, with C. muridarum being more closely related than the others. As has been demonstrated previously (1,6,8,24,44,50,58), no association between genotype and clinical phenotype could be found with ompA, as each of the two major clades contained ocular, genital, and LGV reference strains (Fig. 1A).…”

“…It is also one of the most polymorphic chlamydial genes known (24). It has been proposed that this variability is due to the antigenicity of MOMP and selective pressure of the immune system (6). As a result, the phylogeny of MOMP is not in agreement with tissue tropism or disease.…”

“…Despite MOMP being the immunodominant surface antigen, the phylogenetic categorization of MOMP is not concordant with pathobiotypes or tissue tropism (1,6,8,24,44,50,58). Numerous typing techniques have been applied to C. trachomatis to better understand the epidemiology and pathogenesis of disease.…”

In Vitro Recombinants of Antibiotic-Resistant Chlamydia trachomatis Strains Have Statistically More Breakpoints than Clinical Recombinants for the Same Sequenced Loci and Exhibit Selection at Unexpected Loci

“…The samples in the present study were from San Francisco, California, and Amsterdam, The Netherlands, suggesting that not only are these regions common sites of recombination in the genome, but they are unaffected by geographic perturbations. We and others have also shown the ompA region to be involved in homologous recombination (5,16,17,(20)(21)(22)25) in addition to the trpB or trpA region (20). Only one strain in the current study, D43nl, showed no evidence of recombination despite previous identification of LGT in our MLST study (9).…”

Lymphogranuloma Venereum Prevalence in Sweden among Men Who Have Sex with Men and Characterization ofChlamydia trachomatis ompAGenotypes

“…On the other hand, the association with specific ompA variants could be linked to other genome regions harboring functions for the colonization of different tissues. It has recently been demonstrated that the ompA phylogeny differs significantly from the genetic background represented by housekeeping genes, as well as by intergenic noncoding regions and the pmp family (6). Consequently, the strains with the ompA variants commonly observed in MSM may contain other genes that confer tissue tropism or propensity for colonization.…”