Revolutionizing Quinolone Development for DNA Gyrase Targeting; Discovering the Promising Approach to Fighting Microbial Infections

DNA gyrase is a type II topoisomerase enzyme that can cause negative supercoiling in DNA by using the energy produced by ATP hydrolysis. There are two main types of topoisomerases: type I and type II. Type I enzymes cut a single strand of DNA and are further classified as type IA if they connect to a 5′ phosphate of DNA, or type IB if they link to a 3′ phosphate. Type II topoisomerases break both strands, creating a staggered double-strand break. Antimicrobial resistance is a major concern for the global healthcare system. Resistance is the ability of microorganisms to neutralize and withstand antimicrobial drugs previously used to treat microbial infections. Some known classes of DNA gyrase inhibitors are coumarins, cyclothialidines, and quinolones. Antimicrobial medicines such as quinolones have been widely used to treat microbiological diseases. However, the increased use of quinolones has led to the emergence of quinolone-resistant bacteria, which poses a serious risk to public health. Microorganisms can cause resistance due to changes in the target enzymes, DNA gyrase, and topoisomerase IV, which are responsible for transcription and DNA replication. Additionally, differences in drug entry and efflux may also play a role in resistance. Plasmids that produce the Qnr protein can mediate resistance to quinolones by protecting the quinolone targets from inhibition. This review aims to revolutionize the discovery of quinolone-based antibiotics, specifically targeting DNA gyrase, a critical enzyme in bacterial DNA replication, to enhance the efficacy and specificity of anti-microbail agents against microbial infections.