Supercoiling, topoisomerase inhibition

Correct answer = C. Fluoroquinolones, such as ciprofloxacin, inhibit bacterial DNA gyrase—a type II DNA topoisomerase. This enzyme catalyzes the transient breaking and rejoining of the phosphodiester bonds of the DNA backbone, to allow the removal of positive supercoils during DNA replication. The other enzyme activities mentioned are not affected. Primase synthesizes RNA primers, helicase breaks hydrogen bonds in front of the replication fork, DNA polymerase I removes RNA primers, and DNA igase joins Okazaki fragments. 

Enzyme inhibitors may inhibit the enzymes directly responsible for the formation of nucleic acids. For example, the topoisomerases, a group of enzymes that are responsible for the supercoiling, cleavage and rejoining of DNA, are inhibited by a number of compounds (Figure 7.11). This inhibition is believed to prevent DNA transcription, which ultimately leads to cell death, which explains the use of these drugs to treat cancer. 

Quinolones interfere with the replication mechanism of bacteria by inhibiting essential enzymes such as DNA gyrase (topoisomerase II) and topoisomerase IV, thereby preventing supercoiling and decatenation of the bacterial DNA and the replication of the latter [5-12]. 

A fifth difference between bacterial and human cells involves the enzymes DNA gyrase and topoisomerase IV These enzymes are involved in bacterial DNA synthesis and are responsible for cutting and resealing DNA strands to prevent excessive supercoiling. Because human cells lack these enzymes, drugs that inhibit the enzymes are specifically active against bacteria. 

D. Ciprofloxacin is a fluoroquinolone antibiotic that will inhibit the strand-cutting function of A subunit of DNA gyrase, a bacterial topoi-somerase II that introduces negative supercoils ahead of the rephcation fork. This disrupts DNA replication and repair, transcription, bacterial chromosome separation, and other bacterial processes involving DNA. At much higher concentrations, the type II topoisomerases of eukaryotic cells can be inhibited. 

The fluoroquinolones are bactericidal analogs of nalidixic acid that interfere with bacterial DNA synthesis. They inhibit topoisomerase II (DNA gyrase), blocking the relaxation of supercoiled DNA, required for replication, and topoisomerase responsible for separation of replicated DNA during cell division. 

These agents inhibit the actions of DNA gyrase (topoisomerase II), which is responsible for the supercoiling of bacterial DNA. 

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