Characterisation of genetic diversity within chlamydia trachomatis in high-risk sexual networks

Abstract

Chlamydia trachomatis is the most commonly diagnosed bacterial STI worldwide. Transmission of C. trachomatis within sexual networks is facilitated by high-risk sexual behaviours. C. trachomatis infections are frequently asymptomatic which allows for un-interrupted C. trachomatis transmission within sexual networks. C. trachomatis strains are characterised by their ompA genotype: strains with ompA genotypes A – C are associated with trachoma, D – K with sexually transmitted urogenital infections, and L1 – L3 with Lymphogranuloma venereum (LGV). The ompA gene is a mutational hotspot within the C. trachomatis genome, and extensive sequence variation within ompA has been reported amongst C. trachomatis strains. OmpA genotyping was applied to C. trachomatis DNA extracted from a conjunctival swab collected from a 10 year old female that had migrated to the UK from Afghanistan, to ascertain whether the child was infected with a trachoma-causing strain, or a strain associated with sexually transmitted urogenital tract infections (Chapter 3). Sequencing of the trpA gene was also conducted, as polymorphisms within this gene have been shown to distinguish ocular and genital C. trachomatis strains (Chapter 3). In recent years, multi-locus genotyping systems including multi-locus sequence typing (MLST), multi-sequence typing (MST), and multi-locus variable number tandem repeat (VNTR) analysis (MLVA), have been developed for C. trachomatis. Genotyping systems can elucidate diversity within C. trachomatis strains circulating in sexual networks. Multi-locus genotyping systems were evaluated to determine their suitability for application in a genotyping survey of LGV C. trachomatis strains in London (Chapter 4). The MLVA-ompA genotyping system was applied to genotype LGVpositive clinical specimens from London, to assess genotypic diversity within LGV C. trachomatis strains within this population (Chapter 5). The study detected several distinct LGV MLVA-ompA genotypes, in addition to a hybrid L2b/D ompA genotype that had previously been reported in Portugal. The data collected has added to the knowledge relating to the current LGV epidemic within MSM in the UK. Multi-locus typing systems cannot achieve the resolution provided by whole genome sequencing. Whole genome sequencing can provide insight into the genomic diversity within LGV C. trachomatis strains. Three LGV isolates collected from asymptomatic and symptomatic MSM in Brighton were whole genome sequenced in Chapter 6, to identify any genomic loci or key sequences that may account for the differences in symptomology between the three patients. The study identified several mutations within the genomes of the three isolates. Of these, SNPs were detected within genes associated with intracellular replication of C. trachomatis in the two isolates collected from symptomatic MSM, that were absent from the isolate obtained from an asymptomatic MSM.

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ORCID for Chloe Elizabeth Manning: orcid.org/0000-0003-2428-7731

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