London, Dec 7 (Inditop.com) A potent new antibiotic has opened up completely new ways of knocking out resistant bugs, says a new study.
It is “an exciting find at a time when resistance to existing antibiotics is growing,” said Tony Maxwell, professor at the John Innes Centre (JIC), an institute of the Biotechnology and Biological Sciences Research Council (BBSRC).
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 and so is an ideal, and already established, target for antibiotics. “If you can knock out this enzyme, you have a potential new drug,” says Maxwell, who led the study.
The molecule has two heads that dock into separate pockets in DNA gyrase, and together they are 100 times more powerful than when working individually.
Neither pocket has previously been exploited by antibacterial drugs that target this enzyme. Although bacteria could develop resistance to this mode of action, it might occur less readily than with other antibiotics.
“The fact that there are two pockets means that it might require simultaneous mutations in both pockets for the bacteria to acquire full resistance to the drug, which is much less likely,” explains Maxwell. “You could say that this is a case of two heads being better than one.”
The antibiotic molecule, simocyclinone D8 (SD8), is a currently unexploited natural product made by soil bacteria.
SD8 itself 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, says a JIC release.
The current method of antibiotic drug discovery is to screen protein targets or bacteria against vast libraries of compounds. Any hits are investigated in more detail.
These findings are slated for publication in Science.
