Bristol scientists make antibiotic breakthrough
It is hoped that the new findings will help scientists develop new antibiotics with a much lower risk of resistance.
Scientists from the University of Bristol have used computer simulations to reveal how bacteria are able to destroy antibiotics - a breakthrough which will help develop drugs which can effectively tackle infections in the future.
The researchers focused on the role of enzymes in the bacteria, which split the structure of the antibiotic and stop it working, making the bacteria resistant.
The new findings reveal that it is possible to test how enzymes react to certain antibiotics.
It is hoped the insight will help scientists to choose the best medicines for specific outbreaks and develop new antibiotics with a much lower risk of resistance.
Professor Adrian Mulholland, from Bristol University’s School of Chemistry, said: “We've shown that we can use computer simulations to identify which enzymes break down and spit out carbapenems quickly and those that do it only slowly.
“This means that these simulations can be used in future to test enzymes and predict and understand resistance. We hope that this will identify how they act against different drugs – a useful tool in developing new antibiotics and helping to choose which drugs might be best for treating a particular outbreak.
The Bristol research team used a special Nobel Prize-winning technique called QM/MM - quantum mechanics/molecular mechanics simulations - to learn how enzymes called 'beta-lactamases' react to antibiotics.
The growing resistance to carbapenems is something the researchers specifically want to understand. These are known as the 'last resort' antibiotics for many bacterial infections and superbugs such as E.Coli.
Resistance to carbapenems makes some bacterial infections untreatable, resulting in minor infections becoming very dangerous and potentially deadly.
The computer simulations revealed that the most important stage in the process is when the enzyme 'spits out' the broken down antibiotic. If this happens quickly, then the enzyme is able to go on chewing up antibiotics. If it happens slowly, then the enzyme gets 'clogged up' and can't break down any more antibiotics, meaning that the bacterium is more likely to die.
The rate of this 'spitting out' depends on the height of the energy barrier for the reaction - if the barrier is high, it happens slowly; if it's low, it happens much more quickly.
The paper, ‘QM/MM Simulations as an Assay for Carbapenemase Activity in Class A β-Lactamases’ by Ewa I. Chudyk, Michael A. L. Limb, Charlotte Jones, James Spencer, Marc W. van der Kamp and Adrian J. Mulholland is published in Chemical Communications.
FIVP has shared a survey, inviting those working in independent practice to share their views on the CMA's proposed remedies.
