Whole-genome analysis of diverse Chlamydia trachomatis strains identifies phylogenetic relationships masked by current clinical typing

Abstract

Chlamydia trachomatis is responsible for both trachoma and sexually transmitted infections causing substantial morbidity and economic cost globally. Despite this, our knowledge of its population and evolutionary genetics is limited. Here we present a detailed whole genome phylogeny from representative strains of both trachoma and lymphogranuloma venereum (LGV) biovars from temporally and geographically diverse sources. Our analysis demonstrates that predicting phylogenetic structure using the ompA gene, traditionally used to classify Chlamydia, is misleading because extensive recombination in this region masks true relationships. We show that in many instances ompA is a chimera that can be exchanged in part or whole, both within and between biovars. We also provide evidence for exchange of, and recombination within, the cryptic plasmid, another important diagnostic target. We have used our phylogenetic framework to show how genetic exchange has manifested itself in ocular, urogenital and LGV C. trachomatis strains, including the epidemic LGV serotype L2b.

Plasmid deficiency in urogenital isolates ofChlamydia trachomatisreduces infectivity and virulence in a mouse model

“…The genomes of nvCT serovar E strains E/SW2 and contemporaneous E/SW3 and E/SW4 have been described and published elsewhere (Harris et al ., 2012). When comparing nvCT strain E/SW2 and E/SW3, we previously showed that there were a total of 229 SNPs separating these two strains, 158 of which are found in a 30‐kb region spanning genes SW2 1391 (CTL‐393) to SW2 1601 (CTL‐417) (Harris et al ., 2012).…”

“…When comparing nvCT strain E/SW2 and E/SW3, we previously showed that there were a total of 229 SNPs separating these two strains, 158 of which are found in a 30‐kb region spanning genes SW2 1391 (CTL‐393) to SW2 1601 (CTL‐417) (Harris et al ., 2012). This SNP‐dense region was shown to be a region of recombination and encompasses genes located alongside the plasticity zone or PZ.…”

“…31 SNPs between bases 167 543 and 171 733 of the F/SW4 genome, 26 being located within gene F/SW‐41481 predicted to encode an integral membrane protein and a single SNP in F/SW‐41491 – a FAD‐dependent monooxygenase. Notably, this region overlaps with the putative recombined regions in nvCT serovar E strain E/SW2 (Harris et al ., 2012). The second region of high SNP density contained 92 SNPs found between bases 710 211 and 725 729, affecting a 15‐kb region encompassing 14 genes, F/SW4 6341–6471.…”

“…It is not possible to predict whether any of these SNPs contributed directly to the differences we have observed in the mouse model. However, our observations are quite consistent with the aforementioned in vivo observations of plasmid‐free strains in human disease (Bjartling et al ., 2009; Harris et al ., 2012) and in other animal models (O'Connell et al ., 2007; Carlson et al ., 2008; Olivares‐Zavaleta et al ., 2010; Russell et al ., 2011). Thus, we feel the most logical inference is to attribute the differences seen to presence and function of the plasmid.…”

“…A subset of Illumina reads was assembled using Velvet, version 1.0.12 (Zerbino & Birney, 2008), producing contiguous nucleotide sequences (contigs), which were scaffolded against the genome of strain F/SW4 (EMBL accession no. HE601804) (Harris et al ., 2012), using abacas (Assefa et al ., 2009). The two rRNA operons assembled into a single contigs, which were manually corrected, as were contig boundaries where possible.…”