Research Team Discovers How To Slow Antibiotic Resistance
With the help of computer simulations, a research team from the University of Bristol has found how bacteria destroy antibiotics and how the process can be slowed down. Their breakthrough findings will help in designing future antibiotics that will help minimize the chance of drug resistance.
Carbapenems, known as the ‘last resort’ antibiotics for most bacterial infections, are now susceptible to being broken down by several class A β-lactamases. The team used QM/MM (quantum mechanics/molecular mechanics) dynamics simulations to give them a molecular level-view of how beta-lactamases enzymes react to β-Lactam antibiotics, such as penicillin and especially carbapenems. Resistance to carbapenems can result in minor infections turning into potentially untreatable and lethal illnesses.
The QM/MM simulations showed a possible weak point in the process of the antibiotic breakdown that can be used against the enzyme. After the enzyme has broken down the antibiotic, it spits it out and the remaining bacteria become resistant. If this “spitting out” process happens quickly and smoothly, the enzyme is able to continue breaking down antibiotics. However, if the enzyme gets overloaded, it becomes unable to break down any more antibiotics and renders the bacteria more vulnerable to the drugs.
The researchers said that the rate of pushing out broken antibiotics depends on how high the energy barrier is for the reaction. This means that if the barrier is high, the process happens more slowly, and vice versa.
Professor Adrian Mulholland of 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 team published their findings in the journal Chemical Communications.
Antibacterial resistance, particularly by dangerous infections known as ‘superbugs’, has become a growing threat to public health worldwide. Last month the White House declared war on resistant bacteria strains with the launch of a task force authorized by President Obama to stop the spread of drug resistant bacteria such as staphylococcus and multidrug-resistant tuberculosis.
Many have joined in the battle against antibacterial resistance. These efforts include a team from Massachusetts Institute of Technology (MIT), which is currently developing new technologies, as well as a team from Ball State University and the University of New Mexico developing a new class of drugs that fight bacterial resistance to antibiotics.