GSK's topoisomerase in the hole
Fluoroquinolone antibiotics work by blocking bacterial topoisomerase IIA, but bacterial resistance to this class of drugs is rising faster than new treatments can be developed.1-3 Researchers at GlaxoSmithKline plc now have generated a new class of antibacterial compounds that can block the activity of bacterial topoisomerase IIA via a mechanism that is distinct from that of fluoroquinolones.4
Bacterial topoisomerase IIA is needed to carry out DNA replication: it works to unwind DNA, cleave the double strands and ligate the broken strands back together. Mutations in the two types of bacterial topoisomerase IIA-DNA gyrase and topoisomerase IV-can cause resistance to fluoroquinolones.
The GSK group, led by Michael Gwynn, director of the Antibacterial Discovery Performance Unit, set out to identify and synthesize new inhibitors of the two types of topoisomerase