Division of Infectious Diseases, Department of Medicine II, University Hospital and Medical Center, Freiburg, Germany
Division of Infectious Diseases, Department of Medicine II, University Hospital and Medical Center, Freiburg, Germany.
Antimicrob Agents Chemother. 2021 Jan 20;65(2). doi: 10.1128/AAC.01803-20.
Inactivating in multidrug-resistant with differing sequence types and quinolone resistance-determining mutations reveals remarkably potentiated activity of the first-in-class topoisomerase inhibitors gepotidacin and zoliflodacin. Differences between both structurally unrelated compounds in comparison to fluoroquinolones regarding the selectivity of RND (resistance-nodulation-cell division)-type transporters, efflux inhibitors, and AcrB porter domain mutations were demonstrated. The findings should reinforce efforts to develop efflux-bypassing drugs and provide AcrB targets with critical relevance for this purpose.
在具有不同序列类型和喹诺酮类药物耐药决定突变的多重耐药中，失活揭示了一流拓扑异构酶抑制剂 gepotidacin 和 zoliflodacin 的显著增强活性。与氟喹诺酮类药物相比，这两种结构上无关的化合物在 RND（耐药-结节-细胞分裂）型转运蛋白、外排抑制剂和 AcrB porter 结构域突变的选择性方面存在差异。这些发现应该加强开发外排旁路药物的努力，并为这一目的提供与 AcrB 靶标密切相关的靶点。
