Bacterial DNA is a long, circular molecule packed into a small cell. When the double helix is unwound for replication or transcription, the DNA ahead of the unwinding point becomes overwound (supercoiled), which would stop the process. The enzyme DNA gyrase relieves this tension. It cuts both strands of the DNA, passes another part of the double helix through the gap, and then rejoins the strands. DNA gyrase is a type of topoisomerase found in bacteria.Quinolones, and the newer fluoroquinolones such as ciprofloxacin, inhibit DNA gyrase. They bind to the enzyme while it is attached to cut DNA, and stop it rejoining the strands. As a result:
• DNA replication stops, so the bacteria cannot divide;
• transcription is blocked, so proteins cannot be made;
• broken DNA builds up, which kills the cell.
Fluoroquinolones are therefore bactericidal. They are broad-spectrum, acting against many Gram-positive and Gram-negative bacteria, and are used for infections such as urinary tract infections.Selective toxicity. Human cells do not have DNA gyrase. Our own topoisomerases have a different structure and are affected far less by these drugs, so bacterial DNA is targeted.Resistance can arise from mutations in the genes for DNA gyrase that change the shape of the drug's binding site, or from efflux pumps that remove the drug from the cell. Because fluoroquinolones are broad-spectrum, their use is also linked with Clostridium difficile infection, so they are now prescribed with care.
• DNA replication stops, so the bacteria cannot divide;
• transcription is blocked, so proteins cannot be made;
• broken DNA builds up, which kills the cell.
Fluoroquinolones are therefore bactericidal. They are broad-spectrum, acting against many Gram-positive and Gram-negative bacteria, and are used for infections such as urinary tract infections.Selective toxicity. Human cells do not have DNA gyrase. Our own topoisomerases have a different structure and are affected far less by these drugs, so bacterial DNA is targeted.Resistance can arise from mutations in the genes for DNA gyrase that change the shape of the drug's binding site, or from efflux pumps that remove the drug from the cell. Because fluoroquinolones are broad-spectrum, their use is also linked with Clostridium difficile infection, so they are now prescribed with care.