State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
Clinical Laboratory, Quanzhou Maternity and Children's Hospital, 700 Fengze Street, Quanzhou, Fujian 362000, China.
ACS Infect Dis. 2024 Jun 14;10(6):1970-1979. doi: 10.1021/acsinfecdis.3c00682. Epub 2024 May 31.
Bacterial resistance caused by β-lactamases has been a major threat to public health around the world, seriously weakening the efficacy of β-lactam antibiotics, the most widely used therapeutic agents against infectious diseases. To detect the bacterial resistance to β-lactam antibiotics, particularly specific type of β-lactam antibiotics, in a rapid manner, we report herein a relay-response chemiluminescence assay. This assay mainly consists of two reagents: a β-lactam-caged thiophenol and a thiophenol-sensitive chemiluminescence reporter, both of which are synthetically feasible. The selective hydrolysis of β-lactam by β-lactamase leads to the releasing of free thiophenol, which then triggers the emission of a chemiluminescence signal in a relay manner. Three thiophenol-caged β-lactams, structural analogues of cephalothin, cefotaxime, and meropenem, respectively, have been synthesized. And the application of this assay with these analogues of β-lactam antibiotics allows fast detection of β-lactamase-expressing resistant bacteria and, more impressively, provides detailed information on the resistant scope of bacteria.
β-内酰胺酶引起的细菌耐药性一直是全球公共卫生的主要威胁，严重削弱了β-内酰胺类抗生素作为治疗传染病最广泛使用的治疗药物的疗效。为了快速检测β-内酰胺类抗生素的细菌耐药性，特别是特定类型的β-内酰胺类抗生素的细菌耐药性，我们在此报告了一种接力反应化学发光测定法。该测定法主要由两种试剂组成：β-内酰胺加笼巯基苯和巯基苯敏感化学发光报告物，两者均具有合成可行性。β-内酰胺酶对β-内酰胺的选择性水解导致游离巯基苯的释放，然后以接力方式触发化学发光信号的发射。已经合成了三种巯基苯笼β-内酰胺，分别为头孢噻吩、头孢噻肟和美罗培南的结构类似物。该测定法应用于这些β-内酰胺类抗生素类似物可快速检测表达β-内酰胺酶的耐药菌，更令人印象深刻的是，它提供了有关细菌耐药范围的详细信息。
