DNA gyrase (Staphylococcus aureus) (DNA gyrase)

DNA gyrase is an essential bacterial enzyme in Staphylococcus aureus that manages DNA topology by introducing negative supercoils, which is vital for DNA replication, transcription, and recombination (UniProt P0A0K8). It functions as a heterotetramer consisting of two GyrA subunits, responsible for DNA breakage and rejoining, and two GyrB subunits, which provide energy through ATP hydrolysis (PubMed: 25212101). Quinolone resistance in S. aureus primarily arises from specific mutations within the Quinolone Resistance-Determining Region (QRDR) of the GyrA subunit, such as the S84L or E88K substitutions, which significantly reduce the binding affinity of traditional fluoroquinolones (StatPearls: Fluoroquinolones). These mutations allow the bacteria to survive standard antibiotic treatments, making quinolone-resistant S. aureus a major public health threat, particularly in the context of Methicillin-resistant S. aureus (MRSA) (PubMed: 10516753). Modern drug discovery efforts target this resistant form using Novel Bacterial Topoisomerase Inhibitors (NBTIs) like gepotidacin or advanced quinolones like delafloxacin that maintain potency despite common QRDR mutations by utilizing different binding orientations or additional interactions (PubMed: 30139801).

Other names

DNA topoisomerase IIGyrA/GyrB complexBacterial topoisomerase IIQuinolone-resistant DNA gyrase

Inhibition of DNA ligation by stabilizing the enzyme-DNA cleavage complex, leading to lethal double-strand breaks, or inhibition of the ATPase activity of the GyrB subunit (PubMed: 25212101).