X-ray crystallography aids antibiotics research

The findings could help scientists develop new antibiotics to tackle the bacteria responsible for many hospital- and community-acquired infections.

Using X-ray crystallography, a team of researchers from GlaxoSmithKline (GSK) is said to have captured a snapshot of the new compound latched on to the enzyme topoisomerase.

This enzyme is part of the bacteria’s internal machinery and helps the bacteria produce proteins and replicate. Stopping this enzyme prevents the bacteria from reproducing. Medicines, known as the quinolones, which target the enzyme have been used successfully as antibiotics since 1962; however, bacteria are increasingly developing resistance to them.

By looking at X-ray images, the team is said to have demonstrated that the new investigational medicine attaches to the enzyme in a different place to the quinolones, enabling it to stop the same bacteria that are resistant to these older treatments.

The research is published in the journal Nature, and is the result of two collaborations between GSK and the Wellcome Trust’s Seeding Drug Discovery initiative and the US Defense Threat Reduction Agency (DTRA).

‘We already knew that targeting this enzyme was clinically proven to stop bacteria in their tracks, we just needed to be a bit more inventive in how we attacked it,’ said Michael Gwynn from GSK’s infectious diseases research group. ‘These images and the data showing the efficacy of this compound against a range of bacteria validate our approach, demonstrating that the enzyme can still be blocked even in bacteria already resistant to other antibiotics that work against this same enzyme.’