What cellular enzymes do fluoroquinolones inhibit?
DNA topoisomerases (either DNA gyrase aka topoisomerase II in gram negatives or topoisomerase IV in gram positive)
What is the role of DNA gyrase II versus DNA topoisomerase IV
Bacterial DNA is negatively coiled; DNA gyrase introduces positive supercoiling whereas DNA topoisomerase introduces negative supercoils and decatenates the DNA
Binds to the GyrA-DNA complex and stabilizes it so arrests the progression of coiling and is thus bacteriostatic; later on, due to the accumulation of double stranded breaks, it is bacteriocidal
How does resistance to fluoroquinolones arise?
Mutation of chromosomal target; low level of plasmid-encoded protein sinks common in mycobacteria
Clinical use of fluoroquinolones?
UTIs, prostatitis, pen-resistant STDs, drug resistant M. tuberculosis, community acquired pneumonia, Salmonella and E coli diarrhea