Chlamydia research brings new insight to tackle bacteria

Southampton researchers have made a breakthrough in Chlamydia genetics.

The findings overcome a significant challenge in the field and pave the way for future research that can inform new vaccines or new treatments.

The project, led by the University of Southampton, included support from NIHR Southampton Biomedical Research Centre researcher Dr David Cleary.

The multi-team effort combined expertise from Southampton’s Chlamydia Research Group, the WISH Laboratory, the Wellcome Trust Sanger Institute and Duquesne University.

Challenges of confronting Chlamydia

Chlamydia is the most common bacterial sexually transmitted infection. It causes infertility, pelvic inflammatory disease and chronic pain in women around the world. It is also the most prevalent cause of infectious blindness in developing countries. The best hope to prevent its ongoing spread is through vaccination.

However, research in understanding the bacterium’s biology has been hampered by its unusual developmental cycle. It only grows inside human cells, raising specific technical challenges that make it harder to study.

As a result, scientists have had difficulty in delivering DNA to the bacterial cells – a process that makes analysing gene function much easier.

‘Jumping’ into the genome

In a new study, Southampton researchers introduced a new technique to Chlamydia research. It is called Transposon Directed Insertion Site Sequencing (TraDIS).

This method allows small pieces of DNA to “jump” into the bacterium’s genome at a specific time point in the Chlamydia growth cycle. These then randomly mutate and inactivate genes.

Working with Dr Jade Forster in the Southampton WISH lab, the team applied cutting edge sequencing technology to identify the genes that were mutated.

The study identified 36 unique mutated sites within the Chlamydia genome, gaining proof of principle of the methodology.

The findings will inspire further studies that assess which genes are essential to survival under different growth conditions.

Finding targets for vaccine development

The study was funded by the Wellcome Trust and published in Wellcome Open Research.

Dr Colette O’Neill, study lead, said: “Our work is the first mutagenesis approach that will enable us to mutate each and every gene in the chlamydial genome using a jumping gene called a transposon.

“This will hopefully give us more information on the genes of this important human pathogen, so we can identify which are essential for growth and therefore can become a target for vaccine development or new treatments.”

The success of this project has led to a three-year grant from the Wellcome Trust to refine the technique. This will share the mutants through the Chlamydia Biobank established in Southampton.

Image credit: Rachel Skilton

Confocal microscope image of immunofluorescently stained Chlamydia-infected eukaryotic cells. Green = chlamydia; blue = eukaryotic cell DNA; red = eukaryotic cell membrane.