Antibacterial Resistance via Gyrb24 Targeting

In nature, four mutations confer resistance to coumarins in Escherichia coli strains: Arg 136 to Cys, His or Ser and Gly-164 to Val. All of these mutations are located at the ATP-binding site for the B subunit of the gyrase enzyme. GyrB proteins with these mutations losses their enzymatic activity. Molecular visualizations showed that Arg-136 in gyrB24 is hydrogen bounded through its guanidinium group to the two oxygen atoms in the Coumarin ring. Planning of new compounds with more profound antibiotic activities includes extending the alkyl group at the 5 position of the noviose sugar for the Coumarin. On the other hand, more studies are needed to assess the molecular interactions between comuarins and the host cells to identify specific moieties involved in allergy (jaundice) reactions evoked by the antibiotics.