FLUOROQUINOLONES (MECHANISM)

FQ inhibit the enzyme DNA gyrase
DNA gyrase enzyme nick the ds DNA, introduces negative supercoils & then reseal the nicked ends
This is necessary to prevent excessive positive supercoiling
DNA gyrase consist of two A & two B subunits
A subunit carries out nicking of DNA, B subunit introduce negative supercoils & then A subunit reseal the strands
FQ bind to A subunit & interfere with its strand cutting & resealing function
In gram +ve bacteria, the major target of FQ action is a similar enzyme k/a Topoisomerase IV
Mammalian cell posses an enzyme k/a Topoisomerase II which has very low affinity for FQ, hence low toxicity to host cells
Mechanism of Resistance: Resistance to FQ is slow to develop
Mutation leading to production of DNA gyrase with reduced affinity to FQ