Grant: Project Grant

In 2014, the World Health Organization labeled antibiotic resistance a "global threat" that requires urgent action. This message has been reinforced by many reports including a UK report, which predicts that if no steps are made to curtail antibiotic resistance, an extra 10 million people a year worldwide will die by 2050. The media has captured the essence of this report with the sound bite "Superbugs to kill 'more than cancer' by 2050". The present situation is indeed alarming in that there are no antibiotics to which bacteria have not developed resistance and many bacteria have multiple resistance mechanisms, making infections caused by superbugs nearly impossible to cure. Aggravating the situation is the fact that for economic reasons, the pharmaceutical industry has largely abandoned new antibiotic drug development. To address this pressing healthcare threat, a multi-pronged approach is required. Most importantly, in addition to curtailing the indiscriminate and unnecessary usage of antibiotics, one crucial aspect to pursue is to study the mechanisms by which bacteria resist the effects of antibiotics and exploit this information for the development of new antibiotic therapies that are less impacted by such resistance mechanisms. Therefore, we will examine in atomic detail how superbugs are resistant to two different classes of antibiotics. We know that these bacteria have dedicated enzymes that detoxify many antibiotics, and the research will reveal how this is exactly achieved. We will than take these insights and explore how we can slightly alter the antibiotics by chemical means so that they can no longer be detoxified, while still retaining their antibiotic properties. Complementary, we will also examine if we can prevent the bacterial enzymes from detoxifying the antibiotics in the first place, using a blocking strategy. Either avenue should provide us with new and much needed solutions for treating infections caused by superbugs.