Man's war on 'invincible' bugs gets new boost in 3D

SCOTTISH researchers have made a key breakthrough in understanding how they could tackle the problem of diseases becoming resistant to antibiotics.

The team from Dundee University, along with colleagues in Oxford, have produced the first three-dimensional molecular image showing how a drug binds with the bug it is trying destroy.

It is hoped the finding could lead to new ways of targeting antibiotics to kill diseases, and reduce the growing problem of illnesses becoming resistant to the drugs.

Professor William Hunter, from the College of Life Sciences at Dundee, has been leading the work looking at the bacterium Pseudomonas aeruginosa (P aeruginosa), which can lead to serious diseases and is particularly dangerous for burns victims, people with cystic fibrosis and patients with compromised immune systems.

The researchers used a machine called a synchrotron to study the bug in detail.

The machine - which houses a ring-shaped vacuum tube similar in size to Hampden Park - fires electrons at close to the speed of light around the loop, manipulated by special magnets which produce very intense X-rays.

The X-rays were then used to create an image of the proteins in P aeruginosa which the antibiotic penicillin binds with to allow the drug to kill the bacterium.

By knowing the 3D structure of the antibiotic when it is bound to the protein, scientists were able to see how the drug works and understand how drugs could be modified to overcome resistance.

The researchers, writing in the Journal of Molecular Biology, will now use the knowledge to develop new therapies.

Prof Hunter said: "Pseudomonas aeruginosa is something we're particularly interested in as this causes a lot of problems for people whose immune system is compromised either due to transplant surgery, chemotherapy, people who have HIV/Aids, people who are recovering from burns, and also young people with cystic fibrosis whose lungs struggle to cope with dangerous bacteria."

He added that the objective of the work was to help advance understanding of potential new targets for the development of therapies against such infections which could be "tough beasts to kill".

"Because these organisms are so tough, we need new ideas for drugs, and the way to do that is to find new targets or exploit old targets and come out with new compounds that will hit the old targets," he said.

Prof Hunter said the protein targeted by the antibiotics his team studied had been key in the treatments available.

However, organisms could change and mutate to become resistant.

"This is a medical problem that deserves a solution, and we are looking at several possible pathways of modifying existing drugs to supplement the arsenal of antibiotics," he added.