Scientific Breakthrough Helps Design Antibiotics Of The Future

Scientists have made an astonishing breakthrough that could help with new drugs in the future and tackling infection. They have discovered how to use computer simulations to show how bacteria are able to destroy antibiotics--focusing on the role of enzymes and how they can make the bacteria resistant.

With the help of a Nobel Prize-winning technique called QM/MM - quantum mechanics/molecular mechanics simulations - the Bristol research team was able to gain a molecular-level insight into how enzymes called ‘beta-lactamases' react to antibiotics.

Researchers note that they are specifically working to understand the growing resistane to carbapenems-otherwise known as ‘last resort' antibiotics for many bacterial infections and super bugs such as E. coli. Resistance to this type of bacterial infection can cause an untreatable reaction, resulting in minor infections that may become very dangerous and potentially deadly.

The QM/MM simulations revealed that the most important step in the whole 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 and the bacterium is resistant. If it happens slowly, then the enzyme gets 'clogged up' and can't break down any more antibiotics, so 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.

"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," said professor Adrian Mulholland, from Bristol University's School of Chemistry, in a news release. "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."

More information regarding the findings can be seen via the journal Chemical Communications.