Population-based analysis of ocular<i>Chlamydia trachomatis</i>in trachoma-endemic West African communities identifies genomic markers of disease severity

<jats:title>ABSTRACT</jats:title><jats:p><jats:italic>Chlamydia trachomatis</jats:italic>(<jats:italic>Ct</jats:italic>) is the most common infectious cause of blindness and bacterial sexually transmitted infection worldwide. Using<jats:italic>Ct</jats:italic>whole genome sequences obtained directly from conjunctival swabs, we studied<jats:italic>Ct</jats:italic>genomic diversity and associations between<jats:italic>Ct</jats:italic>genetic polymorphisms with ocular localization and disease severity in a treatment-naïve trachoma-endemic population in Guinea Bissau, West Africa. All sequences fall within the T2 ocular clade phylogenetically. This is consistent with the presence of the characteristic deletion in<jats:italic>trpA</jats:italic>resulting in a truncated non-functional protein and the ocular tyrosine repeat regions present in<jats:italic>tarP</jats:italic>associated with ocular tissue localization. We have identified twenty-one<jats:italic>Ct</jats:italic>non-synonymous single nucleotide polymorphisms (SNPs) associated with ocular localization, including SNPs within<jats:italic>pmpD</jats:italic>(OR=4.07,<jats:italic>p*=0.001</jats:italic>) and<jats:italic>tarP</jats:italic>(OR=0.34,<jats:italic>p*=0.009</jats:italic>). Eight SNPs associated with disease severity were found in<jats:italic>yjfH (rlmB)</jats:italic>(OR=0.13,<jats:italic>p*=0.037</jats:italic>),<jats:italic>CTA0273</jats:italic>(OR=0.12,<jats:italic>p*=0.027</jats:italic>),<jats:italic>trmD</jats:italic>(OR=0.12,<jats:italic>p*=0.032</jats:italic>),<jats:italic>CTA0744</jats:italic>(OR=0.12,<jats:italic>p*=0.041</jats:italic>),<jats:italic>glgA</jats:italic>(OR=0.10,<jats:italic>p*=0.026</jats:italic>),<jats:italic>alaS</jats:italic>(OR=0.10,<jats:italic>p*=0.032</jats:italic>),<jats:italic>pmpE</jats:italic>(OR=0.08,<jats:italic>p*=0.001</jats:italic>) and the intergenic region<jats:italic>CTA0744-CTA0745</jats:italic>(OR=0.13,<jats:italic>p*=0.043</jats:italic>). This study demonstrates the extent of genomic diversity within a naturally circulating population of ocular<jats:italic>Ct</jats:italic>, and the first to describe novel genomic associations with disease severity. These findings direct investigation of host-pathogen interactions that may be important in ocular<jats:italic>Ct</jats:italic>pathogenesis and disease transmission.</jats:p>