Fluoroquinolone

• How do bacteria become resistant to fluoroquinolone?

  Mutates chromosomal genes that alter target enzymes (DNA gyrase & topoisomerase IV)
• How is DNA gyrase altered to become fluroquinolone resistant?

  Mutation in gyrA or B gene -> alters DNA gyrase

  Reduced affinity for fluoroquinolone antibiotic for DNA gyrase

  Organisms becomes resistant
• How is topoisomerase IV altered to become fluoroquinolone resistant?

  Mutation in parC or E gene in Topo IV

  Reduced affinity for fluoroquinolone antibiotic for Topo IV

  Organism becomes resistant
• Fluoroquinolones end in -floxacin
• How do fluoroquinolones work?

  Inhibit the activity of DNA gyrase & topoisomerase IV -> breaks in DNA -> bacterial death
• What is the role of DNA gyrase (normal)?

  DNA supercoiling?
• What is the role of topoisomerase IV (normal)?

  Cuts both strands of DNA simultaneously -> manages tangles & supercoils?
• Some fluoroquinolones have similar affinity & potency against both target enzymes. Mutations in both DNA gyrase & topoisomerase IV are needed for resistance to occur.