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

• DOI: 10.1186/s13073-018-0521-x
• Publication Date: 2018-02-26T15:52:19Z
• Authors: A. R. Last; H. Pickering; C. h. Roberts; F. Coll; J. Phelan; S. E. Burr; E. Cassama; M. Nabicassa; H. M. B. Seth-Smith; J. Hadfield; L. T. Cutcliffe; I. N. Clarke; D. C. W. Mabey; R. L. Bailey; T. G. Clark; N. R. Thomson; M. J. Holland
• Keywords: Genetic Markers; 0301 basic medicine; Endemic Diseases; 610; Chlamydia trachomatis; QH426-470; Polymorphism, Single Nucleotide; Severity of Illness Index; 03 medical and health sciences; 615; Genetics; Humans; Guinea-Bissau; Genome-wide association analysis; Disease severity; Phylogeny; Pathogen genomic diversity; Trachoma; Likelihood Functions; 0303 health sciences; Whole Genome Sequencing; Research; R; Single nucleotide polymorphisms; 3. Good health; Phenotype; Medicine; Conjunctiva; Genome, Bacterial

ABSTRACTChlamydia trachomatis(Ct) is the most common infectious cause of blindness and bacterial sexually transmitted infection worldwide. UsingCtwhole genome sequences obtained directly from conjunctival swabs, we studiedCtgenomic diversity and associations betweenCtgenetic 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 intrpAresulting in a truncated non-functional protein and the ocular tyrosine repeat regions present intarPassociated with ocular tissue localization. We have identified twenty-oneCtnon-synonymous single nucleotide polymorphisms (SNPs) associated with ocular localization, including SNPs withinpmpD(OR=4.07,p*=0.001) andtarP(OR=0.34,p*=0.009). Eight SNPs associated with disease severity were found inyjfH (rlmB)(OR=0.13,p*=0.037),CTA0273(OR=0.12,p*=0.027),trmD(OR=0.12,p*=0.032),CTA0744(OR=0.12,p*=0.041),glgA(OR=0.10,p*=0.026),alaS(OR=0.10,p*=0.032),pmpE(OR=0.08,p*=0.001) and the intergenic regionCTA0744-CTA0745(OR=0.13,p*=0.043). This study demonstrates the extent of genomic diversity within a naturally circulating population of ocularCt, and the first to describe novel genomic associations with disease severity. These findings direct investigation of host-pathogen interactions that may be important in ocularCtpathogenesis and disease transmission.