Ongoing evolution of Chlamydia trachomatis lymphogranuloma venereum: exploring the genomic diversity of circulating strains

Abstract

Lymphogranuloma venereum (LGV), the invasive infection of the sexually transmissible infection (STI) Chlamydia trachomatis , is caused by strains from the LGV biovar, most commonly represented by ompA-genotypes L2b and L2. We investigated the diversity in LGV samples across an international collection over seven years using typing and genome sequencing. LGV-positive samples (n=321) from eight countries collected between 2011 and 2017 (Spain n=97, Netherlands n=67, Switzerland n=64, Australia n=53, Sweden n=37, Hungary n=31, Czechia n=30, Slovenia n=10) were genotyped for pmpH and ompA variants. All were found to contain the 9 bp insertion in the pmpH gene, previously associated with ompA-genotype L2b. However, analysis of the ompA gene shows ompA-genotype L2b (n=83), ompA-genotype L2 (n=180) and several variants of these (n=52; 12 variant types), as well as other/mixed ompA-genotypes (n=6). To elucidate the genomic diversity, whole genome sequencing (WGS) was performed from selected samples using SureSelect target enrichment, resulting in 42 genomes, covering a diversity of ompA-genotypes and representing most of the countries sampled. A phylogeny of these data clearly shows that these ompA-genotypes derive from an ompA-genotype L2b ancestor, carrying up to eight SNPs per isolate. SNPs within ompA are overrepresented among genomic changes in these samples, each of which results in an amino acid change in the variable domains of OmpA (major outer membrane protein, MOMP). A reversion to ompA-genotype L2 with the L2b genomic backbone is commonly seen. The wide diversity of ompA-genotypes found in these recent LGV samples indicates that this gene is under immunological selection. Our results suggest that the ompA-genotype L2b genomic backbone is the dominant strain circulating and evolving particularly in men who have sex with men (MSM) populations.

Sexual transmission of infections across Europe: appraising the present, scoping the future

“…Using stored samples, the first evidence of transmission among MSM was traced to the early 1980s in San Francisco. Genome analyses show that the strains causing LGV among MSM in Europe (UK, Netherlands, Spain) are highly similar to those found in major cities in Australia and North America, pointing to a clonal origin of the epidemic 44…”

“…Genome analyses show that the strains causing LGV among MSM in Europe (UK, Netherlands, Spain) are highly similar to those found in major cities in Australia and North America, pointing to a clonal origin of the epidemic. 44…”

Specific high-resolution scheme to improve understanding of the spatio-temporal dispersion of lymphogranuloma venereum epidemic

“…The phylogenetic analysis of concatenated genes of Klint et al (2007) scheme and our proposed genes revealed that all variants belonged to the L2b lineage, even though some of them have an ompA other than L2b. Moreover, the whole-genome analysis of L-genotypes revealed that all variants belonged to L2b regardless of ompA ( Seth-Smith et al, 2021 ). Previous studies reported that ompA or parts of ompA may be exchanged between CT strains by recombination ( Harris et al, 2012 ; Labiran et al, 2012 ).…”

“…Previous studies reported that ompA or parts of ompA may be exchanged between CT strains by recombination ( Harris et al, 2012 ; Labiran et al, 2012 ). However, a recent study on the diversification of L-variants revealed that the single nucleotide polymorphisms (SNPs) present in the LGV lineage arose by mutation ( Seth-Smith et al, 2021 ).…”

The Impact of Lateral Gene Transfer in Chlamydia

“…Some studies have shown that this could have a clinical impact in terms of virulence and epidemiology ( Somboonna et al., 2011 ; Andersson et al., 2016 ; Hadfield et al., 2017 ; Borges et al., 2019 ). Moreover, the effect of recombination can vary greatly between the four above-mentioned lineages of C. trachomatis , with the ocular strains being less affected than the urogenital lineages and the clonal LGV lineage having undergone no significant re-combination ( Hadfield et al., 2017 ; Seth-Smith et al., 2021 ).…”