Finding a way to defeat drug-resistance is driving many research projects, including at the University of East Anglia where scientists say they are getting closer to solving the problem of antibiotic resistance.
New research has revealed the mechanism by which drug-resistant bacterial cells maintain a defensive barrier, findings that pave the way for a new wave of drugs that kill superbugs by bringing down their defensive walls rather than attacking the bacteria itself. It means that in future, bacteria may not develop drug-resistance at all. Unravelling this mechanism could also help scientists understand more about human cell dysfunctions linked to disorders such as diabetes, Parkinson’s and other neurodegenerative diseases. The team, supported by the Wellcome Trust, used Diamond Light Source, one of the world’s most advanced scientific machines, to investigate a class of bacteria called ‘Gram-negative bacteria’.
Diamond produces intense light 10 billion times brighter than the sun, allowing scientists to explore almost any material in atomic detail. Gram-negative bacteria is particularly resistant to antibiotics because of its cells’ impermeable lipid-based outer membrane. This outer membrane acts as a defensive barrier against attacks from the human immune system and antibiotic drugs. It allows the pathogenic bacteria to survive, but removing this barrier causes the bacteria to become more vulnerable and die. The research team previously found what they describe as an ‘Achilles heel’ in this defensive barrier but how this defensive cell wall is built and maintained – the ‘assembly machinery’ – was unknown until now.
Lead researcher Prof Changjiang Dong, from UEA’s Norwich Medical School, said: “Bacterial multi-drug resistance, also known as antibiotic resistance, is a global health challenge. Many current antibiotics are becoming useless, causing hundreds of thousands of deaths each year. The number of super-bugs is increasing at an unexpected rate. “Gram-negative bacteria is one of the most difficult ones to control because it is so resistant to antibiotics. “All Gram-negative bacteria have a defensive cell wall. Beta-barrel proteins form the gates of the cell wall for importing nutrition and secreting important biological molecules.
“The beta-barrel assembly machinery (BAM) is responsible for building the gates (beta-barrel proteins) in the cell wall. Stopping the beta-barrel assembly machine from building the gates in the cell wall cause the bacteria to die. Our work paves the way for developing new-generation drugs.” The research was funded by the Wellcome Trust. Collaborators included Dr Neil Paterson of Diamond Light Source (UK), Dr Phillip Stansfield from the University of Oxford, and Prof Wenjan Wang of Sun Yat-sen University (China).
