An antibiotic that binds to a well-established target in a novel and unexpected way could be the inspiration for designing new, more potent antibacterial drugs, according to research published recently in the journal Science.
"A completely new way to beat bacteria is an exciting find at a time when resistance to existing antibiotics is growing," said Professor Tony Maxwell from the John Innes Centre (JIC), lead author of the research. The antibiotic molecule slots into pockets in the surface of a bacterial enzyme,
DNA gyrase, and inhibits its activity. Gyrase is essential for bacteria to survive and grow; however, it is not present in humans so is an ideal, already established target for antibiotics.
The antibiotic molecule, simocyclinone D8 (SD8), currently is an unexploited natural product made by soil bacteria. SD8 does not easily penetrate bacterial cells, but it raises the possibility of finding other molecules that fit into the binding pockets, or designing molecules that work by this mechanism but that penetrate cells more easily. "If you can knock out this enzyme, you have a potential new drug," said Professor Maxwell.
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