Gramicidin S identified as a potent inhibitor for cytochrome bd‐type quinol oxidase

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Abstract
Gramicidin S, a cationic cyclic decapeptide, exhibits the potent antibiotic activity through perturbation of lipid bilayers of the bacterial membrane. From the screening of natural antibiotics, we identified gramicidin S as a potent inhibitor for cytochrome bd‐type quinol oxidase from Escherichia coli. We found that gramicidin S inhibited the oxidase with IC50 of 3.5 μM by decreasing V max and the affinity for substrates but showed the stimulatory effect at low concentrations. Our findings would provide a new insight into the development of gramicidin S analogs, which do not share the target and mechanism with conventional antibiotics.