Department of Biology, Carleton University, Ottawa, ON, Canada K1S 5B6.
Department of Biology, Carleton University, Ottawa, ON, Canada K1S 5B6
G3 (Bethesda). 2020 Jan 7;10(1):79-88. doi: 10.1534/g3.119.400199.
In light of the rising prevalence of antimicrobial resistance (AMR) and the slow pace of new antimicrobial development, there has been increasing interest in the development of adjuvants that improve or restore the effectiveness of existing drugs. Here, we use a novel small RNA (sRNA) screening approach to identify genes whose knockdown increases ciprofloxacin (CIP) sensitivity in a resistant strain of 5000 sRNA constructs were initially screened on a S83L background, ultimately leading to 30 validated genes whose disruption reduces CIP resistance. This set includes genes involved in DNA replication, repair, recombination, efflux, and other regulatory systems. Our findings increase understanding of the functional interactions of DNA Gyrase, and may aid in the development of new therapeutic approaches for combating AMR.
鉴于抗菌药物耐药性（AMR）的不断上升和新抗菌药物研发的缓慢步伐，人们越来越关注能够提高或恢复现有药物疗效的佐剂的开发。在这里，我们使用一种新的小 RNA（sRNA）筛选方法来鉴定那些敲低后可增加环丙沙星（CIP）在耐药菌株中敏感性的基因。最初在 S83L 背景下筛选了 5000 个 sRNA 构建体，最终确定了 30 个经过验证的基因，这些基因的缺失可降低 CIP 耐药性。这组基因包括参与 DNA 复制、修复、重组、外排和其他调节系统的基因。我们的发现增加了对抗生素二甲胺四环素的功能相互作用的理解，并可能有助于开发对抗 AMR 的新治疗方法。
