Abstract
Chlamydia trachomatis is a global cause of blinding trachoma and sexually transmitted infections (STIs). We used comparative genomics of the family Chlamydiaceae to select conserved housekeeping genes for C. trachomatis multilocus sequencing, characterizing 19 reference and 68 clinical isolates from 6 continental/subcontinental regions. There were 44 sequence types (ST). Identical STs for STI isolates were recovered from different regions, whereas STs for trachoma isolates were restricted by continent. Twenty-nine of 52 alleles had nonuniform distributions of frequencies across regions (p<0.001). Phylogenetic analysis showed 3 disease clusters: invasive lymphogranuloma venereum strains, globally prevalent noninvasive STI strains (ompA genotypes D/Da, E, and F), and nonprevalent STI strains with a trachoma subcluster. Recombinant strains were observed among STI clusters. Single nucleotide polymorphisms (SNPs) were predictive of disease specificity. Multilocus and SNP typing can now be used to detect diverse and emerging C. trachomatis strains for epidemiologic and evolutionary studies of trachoma and STI populations worldwide.
Highlights
Phylogenetic analysis showed 3 disease clusters: invasive lymphogranuloma venereum strains, globally prevalent noninvasive STI strains, and nonprevalent STI strains with a trachoma subcluster
We found disease-specific single nucleotide polymorphisms (SNPs) and a diversity of new strains including recombinant strains that occurred for ompA relative to housekeeping loci, following up on our recent discovery of this phenomenon at multiple loci in Chlamydiaceae genomes [15,16,17]
On the basis of comparative genomics [20] and comparisons generated by CGView [23], we identified an initial candidate pool of 14 housekeeping genes (Figure 1) present in all 7 genomes with an average BLAST score ratio (BSR) [24] >0.5 for orthologs queried against C. caviae relative to the BLAST score of each sequence against itself
Summary
Multilocus and SNP typing can be used to detect diverse and emerging C. trachomatis strains for epidemiologic and evolutionary studies of trachoma and STI populations worldwide. Unlike the other C. trachomatis MLST schemes, we used complete genomic comparisons of 7 strains from 4 species within the family Chlamydiaceae to identify conserved candidate housekeeping genes across the genomes. We typed a diverse worldwide collection of reference and clinical isolates from trachoma and STI populations, correlating genetic variation with geography and disease phenotype. We found disease-specific single nucleotide polymorphisms (SNPs) and a diversity of new strains including recombinant strains that occurred for ompA relative to housekeeping loci, following up on our recent discovery of this phenomenon at multiple loci in Chlamydiaceae genomes [15,16,17].
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