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) <i>Chlamydia trachomatis</i>, is caused by strains from the LGV biovar, most commonly represented by <i>ompA</i>-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 (<i>n</i>=321) from eight countries collected between 2011 and 2017 (Spain <i>n</i>=97, Netherlands <i>n</i>=67, Switzerland <i>n</i>=64, Australia <i>n</i>=53, Sweden <i>n</i>=37, Hungary <i>n</i>=31, Czechia <i>n</i>=30, Slovenia <i>n</i>=10) were genotyped for <i>pmpH</i> and <i>ompA</i> variants. All were found to contain the 9 bp insertion in the <i>pmpH</i> gene, previously associated with <i>ompA</i>-genotype L2b. However, analysis of the <i>ompA</i> gene shows <i>ompA</i>-genotype L2b (<i>n</i>=83), <i>ompA</i>-genotype L2 (<i>n</i>=180) and several variants of these (<i>n</i>=52; 12 variant types), as well as other/mixed <i>ompA</i>-genotypes (<i>n</i>=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 <i>ompA</i>-genotypes and representing most of the countries sampled. A phylogeny of these data clearly shows that these <i>ompA</i>-genotypes derive from an <i>ompA</i>-genotype L2b ancestor, carrying up to eight SNPs per isolate. SNPs within <i>ompA</i> 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 <i>ompA</i>-genotype L2 with the L2b genomic backbone is commonly seen. The wide diversity of <i>ompA</i>-genotypes found in these recent LGV samples indicates that this gene is under immunological selection. Our results suggest that the <i>ompA</i>-genotype L2b genomic backbone is the dominant strain circulating and evolving particularly in men who have sex with men (MSM) populations.