Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), Nanjing, 211816, P. R. China.
College of Chemistry and Material Engineering, University of Science and Technology of Anhui, Bengbu, 233000, P. R. China.
Angew Chem Int Ed Engl. 2021 Jan 4;60(1):24-40. doi: 10.1002/anie.202006635. Epub 2020 Aug 18.
β-Lactam antibiotics are generally perceived as one of the greatest inventions of the 20 century, and these small molecular compounds have saved millions of lives. However, upon clinical application of antibiotics, the β-lactamase secreted by pathogenic bacteria can lead to the gradual development of drug resistance. β-Lactamase is a hydrolase that can efficiently hydrolyze and destroy β-lactam antibiotics. It develops and spreads rapidly in pathogens, and the drug-resistant bacteria pose a severe threat to human health and development. As a result, detecting and inhibiting the activities of β-lactamase are of great value for the rational use of antibiotics and the treatment of infectious diseases. At present, many specific detection methods and inhibitors of β-lactamase have been developed and applied in clinical practice. In this Minireview, we describe the resistance mechanism of bacteria producing β-lactamase and further summarize the fluorogenic probes, inhibitors of β-lactamase, and their applications in the treatment of infectious diseases. It may be valuable to design fluorogenic probes with improved selectivity, sensitivity, and effectiveness to further identify the inhibitors for β-lactamases and eventually overcome bacterial resistance.
β-内酰胺类抗生素通常被认为是 20 世纪最伟大的发明之一,这些小分子化合物挽救了数百万人的生命。然而,在抗生素的临床应用中,病原菌分泌的β-内酰胺酶会导致药物耐药性逐渐产生。β-内酰胺酶是一种可以高效水解和破坏β-内酰胺类抗生素的水解酶。它在病原菌中快速发展和传播,耐药菌对人类健康和发展构成严重威胁。因此,检测和抑制β-内酰胺酶的活性对于合理使用抗生素和治疗传染病具有重要意义。目前,已经开发和应用了许多针对β-内酰胺酶的特异性检测方法和抑制剂。在这篇综述中,我们描述了产生β-内酰胺酶的细菌的耐药机制,并进一步总结了用于检测β-内酰胺酶的荧光探针、抑制剂及其在治疗感染性疾病中的应用。设计具有改进的选择性、灵敏度和有效性的荧光探针来进一步鉴定β-内酰胺酶抑制剂,最终克服细菌耐药性,可能具有重要价值。