Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain.
Future Med Chem. 2016 Jun;8(10):1133-51. doi: 10.4155/fmc-2016-0027. Epub 2016 Jun 15.
Most efforts in the development of antimicrobials have focused on the screening of lethal targets. Nevertheless, the constant expansion of antimicrobial resistance makes the antibiotic resistance determinants themselves suitable targets for finding inhibitors to be used in combination with antibiotics. Among them, inhibitors of antibiotic inactivating enzymes and of multidrug efflux pumps are suitable candidates for improving the efficacy of antibiotics. In addition, the application of systems biology tools is helping to understand the changes in bacterial physiology associated to the acquisition of resistance, including the increased susceptibility to other antibiotics displayed by some antibiotic-resistant mutants. This information is useful for implementing novel strategies based in metabolic interventions or combination of antibiotics for improving the efficacy of antibacterial therapy.
大多数抗菌药物的研发工作都集中在筛选致死靶点上。然而，抗菌药物耐药性的不断扩展使得抗生素耐药决定因子本身成为寻找抑制剂的合适靶点，这些抑制剂可与抗生素联合使用。其中，抗生素灭活酶和多药外排泵抑制剂是提高抗生素疗效的合适候选药物。此外，系统生物学工具的应用有助于理解与耐药性获得相关的细菌生理学变化，包括一些抗生素耐药突变体对其他抗生素的敏感性增加。这些信息对于实施基于代谢干预或抗生素联合使用的新型策略以提高抗菌治疗的疗效非常有用。
