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

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

Background: Chlamydia trachomatis (Ct) is the most common infectious cause of blindness and bacterial sexually transmitted infection worldwide. Ct strain-specific differences in clinical trachoma suggest that genetic polymorphisms in Ct may contribute to the observed variability in severity of clinical disease.

Methods: Using Ct whole genome sequences obtained directly from conjunctival swabs, we studied Ct genomic diversity and associations between Ct genetic polymorphisms with ocular localization and disease severity in a treatment-naïve trachoma-endemic population in Guinea-Bissau, West Africa.

Results: All Ct sequences fall within the T2 ocular clade phylogenetically. This is consistent with the presence of the characteristic deletion in trpA resulting in a truncated non-functional protein and the ocular tyrosine repeat regions present in tarP associated with ocular tissue localization. We have identified 21 Ct non-synonymous single nucleotide polymorphisms (SNPs) associated with ocular localization, including SNPs within pmpD (odds ratio, OR = 4.07, p* = 0.001) and tarP (OR = 0.34, p* = 0.009). Eight synonymous SNPs associated with disease severity were found in yjfH (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 region CTA0744-CTA0745 (OR = 0.13, p* = 0.043).

Conclusions: This study demonstrates the extent of genomic diversity within a naturally circulating population of ocular Ct and is the first to describe novel genomic associations with disease severity. These findings direct investigation of host-pathogen interactions that may be important in ocular Ct pathogenesis and disease transmission.

Chlamydia trachomatis, Disease severity, Genome-wide association analysis, Pathogen genomic diversity, Single nucleotide polymorphisms, Trachoma
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Last, A.R.
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Pickering, H.
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Roberts, C. h.
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Coll, F.
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Phelan, J.
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Burr, S.E.
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Cassama, E.
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Nabicassa, M.
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Seth-Smith, H.M.B.
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Hadfield, J.
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Cutcliffe, L.T.
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Clarke, I.N.
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Mabey, D.C.W.
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Bailey, R.L.
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Clark, T.G.
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Thomson, N.R.
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Holland, M.J.
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Last, A.R.
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Pickering, H.
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Roberts, C. h.
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Coll, F.
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Phelan, J.
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Burr, S.E.
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Cassama, E.
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Nabicassa, M.
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Seth-Smith, H.M.B.
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Hadfield, J.
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Cutcliffe, L.T.
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Clarke, I.N.
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Mabey, D.C.W.
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Bailey, R.L.
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Clark, T.G.
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Thomson, N.R.
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Holland, M.J.
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Last, A.R., Pickering, H., Roberts, C. h., Coll, F., Phelan, J., Burr, S.E., Cassama, E., Nabicassa, M., Seth-Smith, H.M.B., Hadfield, J., Cutcliffe, L.T., Clarke, I.N., Mabey, D.C.W., Bailey, R.L., Clark, T.G., Thomson, N.R. and Holland, M.J. (2018) Population-based analysis of ocular Chlamydia trachomatis in trachoma-endemic West African communities identifies genomic markers of disease severity. Genome Medicine, 10 (1), 1-19, [15]. (doi:10.1186/s13073-018-0521-x).

Record type: Article

Abstract

Background: Chlamydia trachomatis (Ct) is the most common infectious cause of blindness and bacterial sexually transmitted infection worldwide. Ct strain-specific differences in clinical trachoma suggest that genetic polymorphisms in Ct may contribute to the observed variability in severity of clinical disease.

Methods: Using Ct whole genome sequences obtained directly from conjunctival swabs, we studied Ct genomic diversity and associations between Ct genetic polymorphisms with ocular localization and disease severity in a treatment-naïve trachoma-endemic population in Guinea-Bissau, West Africa.

Results: All Ct sequences fall within the T2 ocular clade phylogenetically. This is consistent with the presence of the characteristic deletion in trpA resulting in a truncated non-functional protein and the ocular tyrosine repeat regions present in tarP associated with ocular tissue localization. We have identified 21 Ct non-synonymous single nucleotide polymorphisms (SNPs) associated with ocular localization, including SNPs within pmpD (odds ratio, OR = 4.07, p* = 0.001) and tarP (OR = 0.34, p* = 0.009). Eight synonymous SNPs associated with disease severity were found in yjfH (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 region CTA0744-CTA0745 (OR = 0.13, p* = 0.043).

Conclusions: This study demonstrates the extent of genomic diversity within a naturally circulating population of ocular Ct and is the first to describe novel genomic associations with disease severity. These findings direct investigation of host-pathogen interactions that may be important in ocular Ct pathogenesis and disease transmission.

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Accepted/In Press date: 13 February 2018
e-pub ahead of print date: 26 February 2018
Published date: 2018
Keywords: Chlamydia trachomatis, Disease severity, Genome-wide association analysis, Pathogen genomic diversity, Single nucleotide polymorphisms, Trachoma

Identifiers

Local EPrints ID: 418667
URI: http://eprints.soton.ac.uk/id/eprint/418667
PURE UUID: 4463ede3-828a-4675-967a-b797e6883a9b
ORCID for I.N. Clarke: ORCID iD orcid.org/0000-0002-4938-1620

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Date deposited: 16 Mar 2018 17:30
Last modified: 26 Nov 2021 02:32

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Contributors

Author: A.R. Last
Author: H. Pickering
Author: C. h. Roberts
Author: F. Coll
Author: J. Phelan
Author: S.E. Burr
Author: E. Cassama
Author: M. Nabicassa
Author: H.M.B. Seth-Smith
Author: J. Hadfield
Author: L.T. Cutcliffe
Author: I.N. Clarke ORCID iD
Author: D.C.W. Mabey
Author: R.L. Bailey
Author: T.G. Clark
Author: N.R. Thomson
Author: M.J. Holland

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