Chlamydia: Silent, Treacherous, Invisible?

Schematic of Chlamydia plasmids, showing  the genes around the outside of the circle. Differences between strains is shown by the marks in concentric circles. Of particular interest is the green bar where DNA has been deleted from the plasmid in one strain. In this case the area that has disappeared are used in medical tests. This deletion makes the bacteria invisible to medical diagnosis. [Credit: Seth-Smith et al. BMC Genomics 2009 10:239   doi:10.1186/1471-2164-10-239]

Schematic of Chlamydia plasmids, showing the genes around the outside of the circle. Differences between strains is shown by the marks in concentric circles. Of particular interest is the green bar where DNA has been deleted from the plasmid in one strain. In this case the area that has disappeared are used in medical tests. This deletion makes the bacteria invisible to medical diagnosis. [Credit: Seth-Smith et al. BMC Genomics 2009 10:239 doi:10.1186/1471-2164-10-239]

04 February 2013

By Helena Seth-Smith

Bacteria that cause the sexual diseases Chlamydia and Gonorrhoea can swap DNA between their peers and hide from medical tests, explains Helena Seth-Smith. Genetic sequencing may help us penetrate their camouflage.

I’m fascinated by the bacterium Chlamydia trachomatis. Known as the silent sexual disease, it is responsible for infections that don’t always produce symptoms, yet can cause serious damage over time. In the UK Chlamydia is best known as a sexually transmitted infection (STI) that is carried by approximately 4% of people. The disease can cause infertility in women who may not even know that they are even carrying the bacterium. A more aggressive form of the disease has been associated with an outbreak of proctitis (inflammation of the anus) among men who have sex with men, and in developing countries, the same bacterium is responsible for trachoma, infectious blindness. .

Chlamydia is very easy to treat – all that is needed is a simple oral antibiotic. The difficulty lies in detecting that someone has an infection. Chlamydia trachomatis is one of the smallest known bacteria and was initially identified as a virus. Using a complex lifecycle, it lives and grows inside the cells of the human host, where hundreds of bacteria are replicated from just one infectious particle

At the Sanger Institute, our initial interest with Chlamydia was to sequence and analyse its genome. In the last couple of years we have found some remarkable properties of this bacterium: despite being encased in a human cell, when it meets another Chlamydia it seems more than happy to swap its DNA!  This is often a good way for bacteria to share diversity and increase fitness, but we were not expecting it to be used to such an extent by such a small, intracellular bacterium. We are now growing the Chlamydia in the laboratory (a tricky task!) and are hoping to expand our research in this area.

After looking at the genomes of a few dozen Chlamydia, we started to wonder about the other major bacterial sexually transmitted infections (STIs), which are Neisseria gonorrhoeae which causes Gonorrhoea, and Treponema pallidum subspecies pallidum which causes Syphilis. We were surprised to find that very little work has been carried out on the genomics of these bacteria.

While these bacteria share little in terms of relationship to each other, they have certain similarities. For example, all are found only in humans, Gonorrhoea bacteria appear to recombine (swap their DNA) as well as Chlamydia, and all have smallish genomes meaning that they may be reliant on the host for many growth requirements.

Of significant clinical concern is an appearing trend of bacteria apparently accidentally losing their diagnostic targets – used in medical tests – and becoming “invisible”. When this happens medical screening of patient samples isn’t always able to identify when a problem exists. This has been seen in one strain of Chlamydia which we studied several years ago, and recently some strains of Gonorrhoea have also lost diagnostic targets, making them harder to detect.

We hope that highlighting this problem of increasing invisibility will encourage the use of more thorough diagnostics where appropriate. We are also hopeful that the next few years will see the introduction of more routine genome sequencing in some clinical laboratories, which will give us vastly more information on the bacteria circulating and will us help to define the problems we face.

Helena Seth-Smith is a Postdoctoral Fellow, in the Population genomics of molecular phenotypes group at the Wellcome Trust Sanger Institute more…

Related Links

Research paper: Seth-Smith H and Thomson NR. Whole-genome sequencing of bacterial sexually transmitted infections: implications for clinicians.Curr Opin Infect Dis. 2013 Feb;26(1):90-8. doi: 10.1097/QCO.0b013e32835c2159
http://www.ncbi.nlm.nih.gov/pubmed/23221768

Sanger Institute Pathogen Genomics Group
http://www.sanger.ac.uk/research/projects/pathogengenomics/

Sanger Institute Global Health Research
http://www.sanger.ac.uk/research/initiatives/globalhealth/

Press Release on Chlamydia: Tracing the UK’s No1 sexually transmitted infection
http://www.sanger.ac.uk/about/press/2012/120311.html