The molecular basis of action of the toxin Microcin B17 on DNA gyrase

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We are in danger of heading for a crisis in infectious diseases. The combined effects of multi-drug-resistant bacterial infections, such as MRSA and C. difficile, and the lack of new antibiotics being produced by pharmaceutical companies, means that academic labs need to make a more significant contribution to solving this problem. We are studying an enzyme from bacteria called DNA gyrase, which is already the target for antibiotics such as Cipro (ciprofloxacin), the drug used to combat anthrax during the scare in the USA in 2001. Unfortunately, due to resistance problems, Cipro is no longer as effective as it was and the search is on for antibiotics to replace it. Microcin B17 is a toxin produced by bacteria to kill other bacteria, and it works in a manner similar to Cipro but is unlikely to be affected by the same resistance problems. We aim to understand the molecular details of how Microcin B17 works such that this information can be used in the future design of new antibiotics that can potentially replace Cipro.