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The University of Southampton

Chlamydia that avoids diagnosis: DNA deletion makes Swedish Chlamydia ‘invisible’

Published: 21 May 2009

New sequencing and analysis of six strains Chlamydia will result in improved diagnosis of the sexually transmitted infection.

A study, published today, provides remarkable insights into a new strain of Chlamydia that was identified in Sweden in 2006 after spreading rapidly across the country by evading most established diagnostic tests.

The results also reveal more about the evolution of the Chlamydia trachomatis bacterium, which is the most common cause of sexually transmitted infections (STIs) globally. The long-term effects of an undetected Chlamydia infection include infertility and ectopic pregnancy. Long-term eye infection by Chlamydia is also the leading cause of preventable blindness in the developing world.

As part of a long-standing collaboration between the University of Southampton and the Wellcome Trust Sanger Institute, the team of researchers focused on six strains of Chlamydia. Of particular interest to the team was the new Swedish strain provided by collaborators at Malmo University Hospital, Sweden.

Professor Ian Clarke, of the University of Southampton and senior researcher in the study said: “This is the first study that uses highly accurate, complete genome sequences to define the nature and extent of variation in Chlamydia trachomatis.”

The genome of the Swedish strain features an evolutionary ‘hiccup’ that allowed it to go undetected in Sweden for several months. Indeed, doctors thought that the numbers of cases of Chlamydia were falling, when the opposite was true. Through non-diagnosis, this version of Chlamydia spread silently. The reason: a deletion of the region of genetic information used to diagnose the presence of Chlamydia.

The deletion, 377 letters of genetic code, occurred on the plasmid of the bacterium. Plasmids are small, circular molecules of DNA that are located outside the chromosome. Chlamydial plasmids have been shown to vary little between different strains of Chlamydia, and are present in larger quantities than the chromosome. This makes them ideal candidate targets for diagnostic tools. Clinical tests have focused on one region of the bacterial plasmid – a gene of unknown function which is largely deleted in the new Swedish strain.

“We have confidently placed great reliance on nucleic acid-based diagnostic tests for many years,” explains Professor Clarke, “but we must always be alert to changes in the biology of this organism. Chlamydia are notoriously difficult to study in the laboratory and genomics can make a vital contribution to adding to our understanding of this insidious parasite.”

After careful analysis of the newly sequenced plasmids of these strains, the team have identified the regions of the plasmid that vary least between strains. “These are thought to be important in the stability of the plasmid, and so tests on these regions should prove more reliable” says co-author Dr Pete Marsh from the Southampton Health Protection Agency.

“This is a truly remarkable turn of events,” adds Dr Nicholas Thomson at the Sanger Institute. “It is an example today of evolution in action: we believe that diagnostic tests that target one region of the Chlamydial plasmid have allowed the Swedish strain, very quickly, to become the dominant strain in that country.”

Chlamydia is a bacterial parasite that only grows within human cells: as a result there is not a great deal of exchange of genetic material between strains. The stability of the link between the bacterial chromosome and the plasmid DNA was also established in this study, reinforcing confidence in the plasmid as the target for diagnostic tests.

“The medical and research communities need to heed this warning,” says Dr Helena Seth-Smith, investigator at the Sanger Institute and lead author on the study. “Chlamydia infections appeared to be in decline in Sweden, but this could not have been further from the truth. The loss of a segment of genetic code made the tests completely powerless to detect this particular strain of Chlamydia.”

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