Casting light on the neglected tropical disease Trachoma

Genomic sequencing reveals link between STIs and leading cause of infectious blindness

Casting light on the neglected tropical disease Trachoma

chlamydia.jpgSpike Walker, Wellcome Images

For the first time, genome sequencing has been carried out on Chlamydia trachomatis (C. trachomatis), a bacteria responsible for the disease Trachoma - the world’s leading infectious cause of blindness, according to a study in Nature Communications.

Researchers at the Wellcome Trust Sanger Institute and Menzies School of Health Research, Australia have discovered that genes can move from chlamydia strains in the eye to sexually transmitted strains of chlamydia, allowing them to then infect the eye and cause Trachoma – a neglected tropical disease.

C. trachomatis is the major cause of sexually transmitted infections (STIs) worldwide and is also responsible for trachoma. Trachoma affects about 2.2 million people worldwide, and is still present in some Indigenous communities in the Northern Territory of Australia.

The clinical impact of the results is that trachoma re-emergence may be more likely than previously thought, particularly if Chlamydia STI remains common.

“This work came about from the analysis of frozen isolates that had been collected in the 1980s and 1990s. We were able to resuscitate chlamydia bacteria that had been frozen for 30 years, and study their genomes to find out how they had evolved.”

Dr Patiyan Andersson, Senior Research Officer at the Menzies School of Health Research (Menzies) and lead author of the paper

The study has resulted in a major change in the understanding of C. trachomatis evolution. It was previously believed that the different version of Chlamydia that caused trachoma were a completely separate lineage from those that cause STIs, this research team has proven otherwise.

The team has provided strong evidence that the acquisition of just one or two gene variants can change an STI causing strain into a Trachoma associated strain. Because it is also now known that Chlamydia can readily exchange DNA this shows that there is a continued potential for new variant Trachoma strains to emerge.

The study was led by Professor Nick Thomson from the Welcome Trust Sanger Institute and Associate Professor Phil Giffard, from Menzies, with important contributions from researchers at the Chlamydia Biobank at the University of Southampton.

“The sequences of these strains were the biggest surprise of my scientific career to date – they were completely different to how they ‘should’ have been. Surprises are what every scientist hopes for. It was very rewarding to work with the same researchers who collected these strains in the Northern Territory in the 1980s, three of whom contributed even though retired, and also to work with our superb collaborators in the UK.”

Associate Professor Giffard from the Menzies School of Health Research

The outcome of this study demonstrates the huge value of long term storage of clinical and biological material, and its analysis with modern high technology. There remain many important unanswered questions about C. trachomatis, which in many ways remains an enigmatic pathogen. However, this study has revealed some of its secrets.

“Genomics has not only unified scientists across the world it has also challenged commonly held beliefs that make us rethink how we are tackling important diseases that have dogged human kind for centuries. Trachoma is a neglected tropical disease and one where the clear benefits of a combined skill set, using both classical and cutting edge techniques, have provided novel insights that are of immediate importance for tackling this disease.”

Professor Nick Thomson, group leader at the Wellcome Trust Sanger Institute

Notes to Editors
Publications
  • Chlamydia trachomatis from Australian Aboriginal people with trachoma are polyphyletic composed of multiple distinctive lineages.

    Andersson P, Harris SR, Seth Smith HM, Hadfield J, O'Neill C et al.

    Nature communications 2016;7;10688

Funding:

The studies commencing in 2012 were supported by Australian National Health, Medical Research Project Grants and the Wellcome Trust.

The studies performed in the 1980s and 1990s were supported by the Australian National Health and Medical Research Council (NHMRC), the Clive and Vera Ramaciotti Foundation, the Channel 10 Children’s Medical Foundation and a Father Frank Flynn Fellowship from the Northern Territory Government.

Participating centres:
  • Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory 0810, Australia
  • Pathogen Genomics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom.
  • Functional Genomics Centre Zürich, University of Zurich, Zurich CH-8057, Switzerland.
  • Institute for Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Zurich CH-8057, Switzerland.
  • Department of Clinical and Experimental Science, Molecular Microbiology Group,
  • University Medical School, Southampton General Hospital, Southampton SO16 6YD, United Kingdom.
  • Melbourne Medical School, The University of Melbourne, Melbourne, Victoria 3010, Australia.
  • Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom.
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