Whole-genome analysis of diverse Chlamydia trachomatis strains identifies phylogenetic relationships masked by current clinical typing

Journal name:
Nature Genetics
Volume:
44,
Pages:
413–419
Year published:
DOI:
doi:10.1038/ng.2214
Received
Accepted
Published online

Abstract

Chlamydia trachomatis is responsible for both trachoma and sexually transmitted infections, causing substantial morbidity and economic cost globally. Despite this, our knowledge of its population and evolutionary genetics is limited. Here we present a detailed phylogeny based on whole-genome sequencing of representative strains of C. trachomatis from both trachoma and lymphogranuloma venereum (LGV) biovars from temporally and geographically diverse sources. Our analysis shows that predicting phylogenetic structure using ompA, which is traditionally used to classify Chlamydia, is misleading because extensive recombination in this region masks any true relationships present. We show that in many instances, ompA is a chimera that can be exchanged in part or as a whole both within and between biovars. We also provide evidence for exchange of, and recombination within, the cryptic plasmid, which is another key diagnostic target. We used our phylogenetic framework to show how genetic exchange has manifested itself in ocular, urogenital and LGV C. trachomatis strains, including the epidemic LGV serotype L2b.

At a glance

Figures

  1. Maximum likelihood reconstruction of the phylogeny of C. trachomatis with recombinations removed.
    Figure 1: Maximum likelihood reconstruction of the phylogeny of C. trachomatis with recombinations removed.

    (a) C. trachomatis species phylogeny using the chromosomal sequences of 52 genomes after predicted recombinations have been removed using a previously described method22. Bootstrap support for nodes on the tree are shown in Supplementary Figure 1. (b) Phylogenetic reconstruction of the C. trachomatis plasmid after the predicted recombinations have been removed. Strain names are colored by serotype. The scale bar indicates the number of SNPs. Plasmid sequences were not available for all the strains shown in a. For comparison, trees without the recombination removal are shown in Supplementary Figure 2.

  2. Reconstruction of recombination events on the species phylogeny of C. trachomatis.
    Figure 2: Reconstruction of recombination events on the species phylogeny of C. trachomatis.

    The top line represents the full chromosome structure of C. trachomatis based on the L2/434/BU strain, with coding sequences represented as blue boxes on the relevant coding strand. The numbers indicate the position in the genome alignment, beginning at CTL0001 (L2/434/BU GenBank accession code AM884176). Each horizontal track represents the chromosome of a strain in the species phylogeny on the left. Blocks shown on the tracks represent the location of received homologous replacements, with their color corresponding to the color of the donor branch on the tree. Tree branches and taxon names are colored by phylogenetic distance, with more similar colors representing more closely related branches. Regions of interest along the genome are highlighted immediately below the recombination tracks. Shown below are plots of the density of non-homoplasic SNP sites, homoplasic SNP sites and recombination events based on a moving window analysis. The window size used was 2,000 bp.

  3. Distribution of SNPs in ompA of C. trachomatis.
    Figure 3: Distribution of SNPs in ompA of C. trachomatis.

    The top line represents the structure of ompA showing the location of variable regions (VS1–VS4, red blocks) and cysteine residues (with conserved residues shown in blue and non-conserved residues shown in orange). On the left is the species phylogeny of C. trachomatis with strain names colored by serotype. Adjacent to each strain name is a track with a background color based on the serotype of the corresponding strain. The c vertical lines along the tracks represent bases that differ from the ancestral sequence (gray, non-homoplasic change), and colored lines represent homoplasic bases (red, A; blue, T; green, C; orange, G). The pattern of the lines provides a barcode of ompA similarity between the strains.

Accession codes

Referenced accessions

NCBI Reference Sequence

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Author information

Affiliations

  1. Pathogen Genomics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.

    • Simon R Harris,
    • Helena M B Seth-Smith,
    • Julian Parkhill &
    • Nicholas R Thomson
  2. Molecular Microbiology Group, University Medical School, Southampton General Hospital, Southampton, UK.

    • Ian N Clarke,
    • Lesley T Cutcliffe &
    • Rachel J Skilton
  3. Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.

    • Anthony W Solomon,
    • Martin J Holland,
    • David Mabey,
    • Rosanna W Peeling &
    • David A Lewis
  4. Health Protection Agency, Public Health Laboratory Southampton, Southampton General Hospital, Southampton, UK.

    • Peter Marsh
  5. Sexually Transmitted Infections Reference Centre, National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa.

    • David A Lewis
  6. Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

    • David A Lewis
  7. Department of Infectious Disease Epidemiology, Imperial College, St. Mary's Hospital Campus, London, UK.

    • Brian G Spratt
  8. Department of Laboratory Medicine and Clinical Microbiology, National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sweden.

    • Magnus Unemo
  9. Department of Laboratory Medicine, Clinical Microbiology, Malmö University Hospital, Malmö, Sweden.

    • Kenneth Persson
  10. Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Malmö University Hospital, Malmö, Sweden.

    • Carina Bjartling
  11. British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.

    • Robert Brunham
  12. Department of Dermatology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.

    • Henry J C de Vries
  13. Sexually Transmitted Infections Outpatient Clinic, Infectious Diseases Cluster, Public Health Service Amsterdam, Amsterdam, The Netherlands.

    • Henry J C de Vries
  14. Centre for Infection and Immunity Amsterdam, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.

    • Henry J C de Vries
  15. Department of Medical Microbiology of Infection Prevention, Laboratory of Immunogenetics, VU University Medical Center, Amsterdam, The Netherlands.

    • Servaas A Morré
  16. Department of Genetics and Cell Biology, Institute of Public Health Genomics, School for Public Health and Primary Care and School for Oncology & Developmental Biology, Faculty of Health, Medicine & Life Sciences, University of Maastricht, Maastricht, The Netherlands.

    • Servaas A Morré
  17. Geneeskundige en Gezondheidsdienst Amsterdam (GGD; Health Service Amsterdam), Amsterdam, The Netherlands.

    • Arjen Speksnijder
  18. Université de Bordeaux, Unité Sous Contrat (USC) Mycoplasmal and Chlamydial Infections in Humans, French National Reference Center for Chlamydial Infections, Bordeaux, France.

    • Cécile M Bébéar,
    • Maïté Clerc &
    • Bertille de Barbeyrac
  19. Institut National de la Recherche Agronomique, USC Mycoplasmal and Chlamydial Infections in Humans, French National Reference Center for Chlamydial Infections, Bordeaux, France.

    • Cécile M Bébéar,
    • Maïté Clerc &
    • Bertille de Barbeyrac

Contributions

S.R.H. assembled, aligned and analyzed the data and wrote the paper. I.N.C. jointly conceived of the project with N.R.T. and provided samples. H.M.B.S.-S. performed experiments, carried out analyses of the data and helped write the paper. L.T.C., P.M., R.J.S., M.J.H., D.M., R.W.P., D.A.L., M.U., K.P., C.B., R.B., H.J.C.d.V., S.A.M., A.W.S., C.M.B., A.S., M.C. and B.d.B. collected and cultured samples. B.G.S. and J.P. helped interpret the data and write the paper. N.R.T. conceived of and ran the project and wrote the paper.

Competing financial interests

The authors declare no competing financial interests.

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