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News of World Medicine

Scientists from Johns Hopkins University have carried out a study on quinolone antibiotics. They are used for some bacterial infections and tuberculosis as well. Quinolones inhibit bacterial enzymes, such as gyrase and topoisomerase IV. This prevents DNA replication and RNA synthesis required for growth.

Previous studies have identified one mechanism of resistance, which is caused by the production of pentapeptide repeat proteins (PRPs), a family of molecules acting as inhibitors of DNA gyrase. One of them, called MfpA, confers resistance to quinolones, the causative agent of tuberculosis (Mycobacterium tuberculosis). Scientists have decided in the course of a new study to reveal how PRP, in particular MfpA, acts at the molecular level. They removed MfpA from Mycobacterium smegmatis after determining that such bacterium could inhibit the supercoiling reaction of DNA gyrase, which is a target of quinolones. In further studies, it is already clear that MfpA can prevent the inhibition of gyrase by quinolones, thus protecting the bacterial cell from the antibiotic. This study will help to find new ideas for drug development.

Source: SCIENCE DAILY