Topoisomerases are essential enzymes that regulate DNA super…
Topoisomerases are essential enzymes that regulate DNA supercoiling in cells. In Escherichia coli, at least four distinct topoisomerases (I–IV) contribute to the maintenance of DNA topology. These enzymes are classified into two types based on their mechanism of action. Type I topoisomerases, which include topoisomerase I and topoisomerase III, function by cleaving a single strand of DNA to relieve negative supercoils, thereby increasing the linking number (Lk). In contrast, type II topoisomerases, which include topoisomerase II (also known as DNA gyrase) and topoisomerase IV, introduce negative supercoils by cleaving both strands of DNA in an ATP-dependent manner, decreasing Lk. The primary role of DNA gyrase is to introduce negative supercoils, which is essential for DNA replication and transcription by reducing torsional stress ahead of replication forks and transcription complexes. Topoisomerase IV, another type II enzyme, plays a crucial role in chromosome segregation by resolving catenated (interlinked) DNA molecules that form during replication. Disruptions in topoisomerase function can severely impact cellular processes. For example, quinolone antibiotics such as ciprofloxacin inhibit DNA gyrase and topoisomerase IV, preventing bacterial DNA replication and leading to cell death. Additionally, mutations in topoisomerase genes can lead to resistance to these antibiotics, which poses challenges for bacterial infection treatment. During a bacterial infection, a patient is given ciprofloxacin, a fluoroquinolone antibiotic that targets topoisomerase II enzymes. Which of the following mechanisms is the MOST plausible way in which a resistant strain of E. coli could evade ciprofloxacin’s effects?