Supercomputers used in arms race with antibiotic resistance

Antibiotic resistance emerges when bacteria develop the ability to overcome the drugs designed to kill them, threatening many medical procedures dependent on the ability to treat infections with antibiotics, such as organ transplants. Every year, approximately 700,000 people are estimated to die due to infection by antibiotic-resistant bacteria, with this number expected to rise into the millions in coming years.

Without effective antibiotics, life expectancy could drop by 20 years, prompting urgent efforts to develop new antibiotics faster than microbes can mutate and form new defences.

A team of researchers from around the world, co-led by the University of Portsmouth’s Dr Gerhard Koenig, are using supercomputers to fight the threat. The scientists are redesigning existing antibiotics to keep up with the changing nature of infection.

“Antibiotics are one of the pillars of modern medicine and antibiotic resistance is one of the biggest threats to human health,” said Koenig, a computational chemist. “There’s an urgent need to develop new ways of fighting ever-evolving bacteria.

“Developing a new antibiotic usually involves finding a new target that is essential for the survival of a wide range of different bacteria. This is extremely difficult, and only very few new classes of antibiotics have been developed in recent times.

“We have taken a simpler approach by starting from an existing antibiotic, which is ineffective against new resistant strains, and modifying it so it’s now able to overcome resistance mechanisms.”

The team includes Nobel laureate Professor Ada Yonath, who shared the Nobel Prize in Chemistry in 2009 for her work on the structure and function of the ribosome. The research was carried out at the Max-Planck-Institut für Kohlenforschung, the Weizmann Institute, and the Universities of Duisburg-Essen, Bochum and Queensland.

The computational approach involves simulating several aspects of a redesigned antibiotic at once, including solubility, effectiveness at penetrating the bacteria, and effectiveness at blocking bacterial protein production.

The researchers’ best drug candidate – which has not yet undergone clinical trials – could be up to 56 times more active for the tested bacterial strains than two antibiotics on the World Health Organisation’s list of essential medicines, erythromycin and clarithromycin. Although the computational work was carried out in a matter of weeks, the team then spent several years verifying experimentally that their approach to the problem was correct.

Koenig said: “Not only is our best candidate more effective against the tested targets, but it also shows activity against the three top ranked bacteria from the WHO priority list where the tested existing antibiotics don’t work. It’s only a matter of time until bacteria develop counterstrategies against our counterstrategies and become resistant to the new antibiotic, so we will have to keep on studying bacterial resistance mechanisms and develop new derivatives accordingly.”

The aim of the study is to show that the resistance mechanisms of bacteria can be addressed in a systematic way, allowing scientists to keep ahead of the changing infections with a computational evolution of new antibiotics.

“Our computers are becoming faster with every year," said Koenig. "So, there is some hope that we will be able to turn the tide. If computers can beat the world champion in chess, I don’t see why they should not also be able to defeat bacteria.”