Breakthrough against antibiotic resistance

A breakthrough in the race to solve antibiotic resistance has been made by a team from the University of East Anglia and Diamond Light Source. The powerful beams of light generated by Diamond allowed the team to study bacteria in extreme detail, enabling them to identify an innovative method to disable the cells and prevent antibiotic resistance. The research, published in Nature, reveals how bacteria are able to construct the camouflage they use to evade the immune system and paves the way for blocking the process through new classes of antibiotics. The work focussed on Gram-negative bacteria which include species like E. coli, salmonella and gonorrhoea. The outer surface of the bacteria acts as a protective cloak against toxic compounds and helps it dodge detection by the body’s defences. Using Diamond, researchers studied this at an atomic level to pinpoint the structure of the integral protein responsible for the final stage of creating the bacteria’s camouflage. By determining the shape of the protein, researchers are now able to design drugs that fit into the protein, stopping it in its tracks, and killing the superbug by disabling the camouflage. “This is an exciting structure that fundamentally advances our understanding of basic cell assembly and at the same time provides a detailed view of an intriguing target for new classes of antibiotics,” said Dr Neil Paterson of Diamond. The findings are important because targeting this final stage of the camouflage assembly mechanism may be possible from the cell exterior, preventing the bacteria from pumping the antibiotic back out and negating a key antibiotic resistance mechanism. “We have identified the path and gate used by the bacteria to transport the barrier building blocks to the outer surface. Importantly, we have demonstrated that the bacteria would die if the gate is locked,” said group leader Professor Changjiang Dong, from UEA’s Norwich Medical School. “This is really important because drug-resistant bacteria are a global health problem. Many current antibiotics are becoming useless, causing hundreds of thousands of deaths each year. The number of super-bugs are increasing at an unexpected rate. This research provides the platform for urgently-needed new generation drugs.” Structural basis for outer membrane lipopolysaccharide insertion