Syphilis, gangrene and tuberculosis killed millions until British scientist Alexander Fleming discovered the first antibiotic. However, the bugs are fighting back, evolving so that they become resistant to even the most powerful modern antibiotics.The rise of so-called superbugs, which can repel even the most powerful modern antibiotics, has set alarm bells ringing. To make matters worse, there hasn’t been a new antibiotic since 2003, leaving the world unprepared to tackle an epidemic.Over the past four years, more than a third of EU countries have experienced a significant increase in drug-resistant E. coli and klebsiella, a bacteria which can cause pneumonia. Globally, there are about 440 000 new cases of multidrug-resistant tuberculosis each year, causing at least 150 000 deaths, according to the World Health Organization.The EU has teamed up with the pharmaceutical industry in the EUR 2 billion Innovative Medicines Initiative, Europe’s largest public-private partnership, to help stimulate the development of new drugs. However, alongside that, it is funding research to try to work out how to slow down the evolution of drug-resistant bacteria.Scientists now believe they have found a way to slow down the rate of evolution by recycling drugs rather than just prescribing the newest one.‘The goal is to use antibiotics in more clever ways to prevent resistance from evolving, for example by recycling the use of alternative antibiotics in a hospital,’ Dr Craig MacLean, from the University of Oxford’s Department of Zoology, said.It means that, rather than the most popular antibiotics, patients could routinely be prescribed alternative, less commonly used antibiotics, to keep bacteria on its toes.Dr MacLean is heading up RESISTEVO, a EUR 1.2 million projectfunded by the European Research Council (ERC)that is recreating the evolution of drug-resistant bacteria in the laboratory to study exactly how the process works.‘This approach allows scientists to observe and manipulate bacterial evolution in real time, providing an unparalleled opportunity to observe resistance evolution in action and to determine the ecological and genetic drivers of resistance,’ Dr MacLean said.‘We hope that, by better understanding the fundamental molecular and population-level processes that influence the evolution of antibiotic resistance, it will be possible to design improved treatment schemes for preventing resistance.’Critical risksThe UK’s chief medical officer, Professor Sally Davies, said earlier this year that the rise of drug resistant bacteria should be ranked alongside terrorism and climate change on the list of critical risks faced by society, and the rise in antibiotic resistance was discussed at a meeting of the G8 group of leading countries in June.Across the world, scientists are searching for ways to slow down the evolution of bacteria, and to find new drugs to replace the ones that no longer work.The EVOLOME project, backed by an EUR 1.5 million ERC Starting grant, will study how global factors might contribute to the ability of bacteria to fight even the strongest of drugs. The team, led by Dr Nathalie Balaban from the Hebrew University of Jerusalem, will develop a methodology for observing evolution of antibiotic resistance that could revolutionize the field and pave the way for similar studies on different microorganisms and pathogens.Another EU-funded project called RARE is trying to slow down or stop the formation of antibiotic resistance by studying how resistance evolves in the laboratory.“‘The goal is to use antibiotics in more clever ways to prevent resistance from evolving, for example by recycling the use of alternative antibiotics in a hospital.’Dr Craig MacLean, Department of Zoology, University of Oxford, UKDynamics of evolution‘We believe that revealing the resistance mechanisms at the molecular level and understanding the dynamics of evolution at population level is the key for finding efficient drug therapies,’ RARE’s principal investigator, Dr Erdal Toprak of Sabanci University in Istanbul, said. ‘Using laboratory evolution experiments and next generation sequencing technologies we can investigate the rules of resistance evolution.’Part of the problem is that the use of antibiotics is not regulated in some countries, leading to overuse, he said, adding that it was not just a matter of discovering new drugs as even brand new ones are prone to the same problem when used inappropriately.‘This is a very big problem that has multiple components including the health policy of countries – in many the use of antibiotics is not regulated – increased mobility, and global poverty,’ he said, adding that the MRSA superbug kills more people than HIV in the US.‘Our efforts may appear quite humble when compared to the significance of the problem, but this does not mean they cannot still have a meaningful impact on efforts to tackle antibiotic resistance,’ he said.
This article was originally published in Horizon, the EU Research and Innovation magazine.