Groundwater Paul W, Xu Sophia, Lai Felcia, Váradi Linda, Tan Jinlong, Perry John D, Hibbs David E
Faculty of Pharmacy, The University of Sydney, Camperdown Campus, Sydney, NSW 2006, Australia.
Department of Microbiology, Freeman Hospital, Newcastle Upon Tyne, UK.
Future Med Chem. 2016 Jun;8(9):993-1012. doi: 10.4155/fmc-2016-0015. Epub 2016 Jun 2.
Since its discovery in 2008, New Delhi metallo-β-lactamase-1 (NDM-1)-producing Enterobacteriaceae have disseminated globally, facilitated predominantly by gut colonization and the spread of plasmids carrying the bla NDM-1 gene. With few effective antibiotics against NDM-1 producers, and resistance developing to those which remain, there is an urgent need to develop new treatments. To date, most drug design in this area has been focused on developing an NDM-1 inhibitor and has been aided by the wealth of structural and mechanistic information available from high resolution x-ray crystallography and molecular modeling. This review aims to summarize current knowledge regarding the detection of NDM-1 producers, the mechanism of action of NDM-1 and to highlight recent attempts toward the development of clinically useful inhibitors.
自2008年发现以来,产新德里金属β-内酰胺酶-1(NDM-1)的肠杆菌科细菌已在全球传播,主要通过肠道定植以及携带bla NDM-1基因的质粒传播。针对产NDM-1细菌的有效抗生素很少,并且对现有抗生素的耐药性不断发展,因此迫切需要开发新的治疗方法。迄今为止,该领域的大多数药物设计都集中在开发NDM-1抑制剂上,高分辨率X射线晶体学和分子建模提供的大量结构和机制信息对此起到了辅助作用。本综述旨在总结有关产NDM-1细菌检测、NDM-1作用机制的现有知识,并重点介绍近期开发临床有用抑制剂的尝试。