Quinolones are a group of broad-spectrum antibiotics that specifically target topoisomerase. Explain how this contributes to cell death in bacteria. Would you expect these drugs to kill hyperthermophilic prokaryotes too? Why or why not?

Question

What will be an ideal response?

Answer 1

Supercoiled DNA exists naturally in circular chromosomes of bacteria, but it can become "overwound"—as it does during DNA replication. Overwinding puts unsustainable torsional stress on DNA, and if the stress is not relieved, DNA will break at random. Supercoiled DNA is partially unwound by topoisomerases that relax supercoiled DNA in a controlled manner. If you inhibit topoisomerase, the cell cannot correct overwinding and the chromosome breaks, causing DNA damage and cell death. You might expect that these drugs would not necessarily kill the hyperthermophilic bacteria, because most organisms exhibit negative supercoiling and have those types of topoisomerases. The hyperthermophiles exhibit positive supercoiling, which is induced by specialized topoisomerases that are not the same ones involved in negative supercoiling. Thus, depending on how specific the quinolones' mode of action may be, negative but not positive supercoiling can be inhibited.