Department of Medicinal Chemistry, Center for Natural Products, Drug Discovery and Development (CNPD3), College of Pharmacy , University of Florida , Gainesville , Florida 32610 , United States.
J Med Chem. 2019 Sep 12;62(17):7618-7642. doi: 10.1021/acs.jmedchem.9b00370. Epub 2019 Apr 18.
Bacteria utilize multiple mechanisms that enable them to gain or acquire resistance to antibiotic therapies during the treatment of infections. In addition, bacteria form biofilms which are surface-attached communities of enriched populations containing persister cells encased within a protective extracellular matrix of biomolecules, leading to chronic and recurring antibiotic-tolerant infections. Antibiotic resistance and tolerance are major global problems that require innovative therapeutic strategies to address the challenges associated with pathogenic bacteria. Historically, natural products have played a critical role in bringing new therapies to the clinic to treat life-threatening bacterial infections. This Perspective provides an overview of antibiotic resistance and tolerance and highlights recent advances (chemistry, biology, drug discovery, and development) from various research programs involved in the discovery of new antibacterial agents inspired by a diverse series of natural product antibiotics.
细菌利用多种机制，使其在感染治疗过程中获得或获得对抗生素治疗的抗性。此外，细菌形成生物膜，这是一种表面附着的富集群落，其中包含被生物分子的保护性细胞外基质包裹的休眠细胞，导致慢性和反复出现的抗生素耐药感染。抗生素耐药性和耐受性是全球性的主要问题，需要创新的治疗策略来应对与致病菌相关的挑战。从历史上看，天然产物在为临床带来新的治疗方法以治疗危及生命的细菌感染方面发挥了关键作用。本观点概述了抗生素耐药性和耐受性，并强调了受各种天然产物抗生素启发的发现新抗菌剂的各个研究计划在化学、生物学、药物发现和开发方面的最新进展。
