Aminocoumarin-resistant DNA topoisomerases
Resistance to aminocoumarins can be a result of direct mutation of the target enyzmes, the DNA gyrases. DNA gyrases are a subclass of DNA topoisomerases, specifically DNA topoisomerase II. The gyrases cut both strands of DNA, relax the supercoiling of the DNA (by introducing negative supercoils), then reanneal the two DNA strands. This relaxation of supercoiling and tangling of the DNA is necessary for cell proliferation. Resistance occurs via mutation in the DNA gyrase that decreases the binding affinity of the aminocoumarin antibiotic to its binding site on the DNA gyrase, allowing ATP to outcompete the drug for competitive binding.