New drug targets could advance fight against sexually transmitted disease chlamydia

Scientists have identified two genes involved in the body's fight against chlamydia. Their findings could lead to the development of new drugs to treat what is now one of the most common sexually transmitted infections (STIs) in the world.

Chlamydia is passed on through unprotected sex and it mainly affects young people under the age of 25. Every year, about 200,000 people test positive for chlamydia in the UK.

Chlamydia is a 'silent disease' as it is asymptomatic for a majority of people. If left untreated, however, it may lead to long-term health problems and to infertility. Chlamydia trachomatis, the bacteria responsible for the infection, can also cause blindness.

Although it is usually well-treated with a short-course of antibiotics, the threat of growing antibiotic resistance is real and may prevent future efforts to get rid of the disease. In 2016, the World Health Organisation issued new guidelines for the treatment of chlamydia, emphasising this problem.

There is therefore a need to develop new treatments, but in order to do so, scientists first must understand the interactions between the infection and the immune system.

In a study – now published in the journal Nature Communications – a team has attempted to find novel drug targets for chlamydia, using an innovative infection model and the genome-editing technique known as CRISPR/Cas9.

Infection model

Few robust in vitro model exist today to allow scientists to study the chlamydia infection. So here, the scientists designed a new model of chlamydia infection, creating macrophages (a type of white blood cells) from human pluripotent stem cells.

During an infection, macrophages play a central role in killing the bacteria and limiting the spread of the infection.

The scientists used the macrophages created from stem-cells to study the macrophage-chlamydia interaction in vitro. They hoped that this would improve their understanding of how host genetics influence the response of macrophages to the pathogen.

"Chlamydia is tricky to study because it can permeate and hide in macrophages where it is difficult to reach with antibiotics. Inside the macrophage, one or two chlamydia cells can replicate into hundreds in just a day or two, before bursting out to spread the infection. This new system will allow us to understand how chlamydia can survive and replicate in human macrophages and could have major implications for the development of new drugs", Dr Amy Yeung, first author from the Wellcome Trust Sanger Institute, said.

To find out more about macrophages' ability to ward off infection, the scientists used CRISPR/Cas9 to genetically edit human induced pluripotent stem cells. They then analysed how their genetic manipulations impacted the macrophages' action.

Two genes - IRF5 and IL-10RA - were identified as playing a key role in the macrophages' response to the infection. They helped limit the chlamydia infection and, when they were switched off – with the help of CRISPR/Cas9 – the macrophages were more susceptible to chlamydia.

These two genes may be drug targets for future chlamydia treatments. The scientists also say that their model could be used to study the interaction between the immune system and other pathogens.