Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK.
Future Med Chem. 2021 Jan;13(2):143-155. doi: 10.4155/fmc-2020-0310. Epub 2021 Jan 7.
Antimicrobial resistance is a pressing threat to global health, with multidrug-resistant pathogens becoming increasingly prevalent. The bacterial SOS pathway functions in response to DNA damage that occurs during infection, initiating several pro-survival and resistance mechanisms, such as DNA repair and hypermutation. This makes SOS pathway components potential targets that may combat drug-resistant pathogens and decrease resistance emergence. This review discusses the mechanism of the SOS pathway; the structure and function of potential targets AddAB, RecBCD, RecA and LexA; and efforts to develop selective small-molecule inhibitors of these proteins. These inhibitors may serve as valuable tools for target validation and provide the foundations for desperately needed novel antibacterial therapeutics.
抗微生物药物耐药性是对全球健康的紧迫威胁，具有多重耐药性病原体的情况日益普遍。细菌 SOS 途径在感染过程中发生 DNA 损伤时发挥作用，启动几种生存和耐药机制，如 DNA 修复和超突变。这使得 SOS 途径成分成为可能的靶点，这些靶点可能对抗耐药性病原体并减少耐药性的出现。本综述讨论了 SOS 途径的机制；潜在靶点 AddAB、RecBCD、RecA 和 LexA 的结构和功能；以及开发这些蛋白质选择性小分子抑制剂的努力。这些抑制剂可以作为有价值的靶标验证工具，并为急需的新型抗菌治疗方法提供基础。
