Targeting bacterial topoisomerases: how to counter mechanisms of resistance.
DNA gyrase and topoisomerase IV are type IIA bacterial topoisomerases that are targeted by highly effective antibiotics. However, resistance via multiple mechanisms arises to limit the efficacies of these drugs. Continued research on type IIA bacterial topoisomerases has provided novel approaches to counter the most common resistance mechanism for utilization of these proven targets in antibacterial therapy. Bacterial topoisomerase I is being explored as an alternative target that is not expected to show cross-resistance. Dual targeting or combination therapy could be strategies for circumventing the development of resistance to topoisomerase-targeting antibiotics. Bacterial topoisomerases are high-value bactericidal targets that could continue to be exploited for antibacterial therapy, if new tactics to counter resistance can be adopted.
Department of Chemistry & Biochemistry, Florida International University, 11200 SW 8 Street, Miami, FL 33199, USA.|Biomolecular Sciences Institute, Florida International University, 11200 SW 8 Street, Miami, FL 33199, USA.
Yuk-Ching
YC
Tse-Dinh
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000201:enzymology; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D026942:DNA Topoisomerases / Q000378:metabolism*; D055808:Drug Discovery; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination; D006801:Humans; D059003:Topoisomerase Inhibitors / Q000737:chemistry / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D059003:Topoisomerase Inhibitors; D026942:DNA Topoisomerases
antibiotic resistance; antibiotics; bactericidal; gyrase; supercoiling; topoisomerase; topoisomerase poisons