Ma Chi-Wang, Ng Kenneth King-Hei, Yam Bill Hin-Cheung, Ho Pak-Leung, Kao Richard Yi-Tsun, Yang Dan
Morningside Laboratory for Chemical Biology, Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
Department of Microbiology and Carol Yu Centre for Infection, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
J Am Chem Soc. 2021 May 12;143(18):6886-6894. doi: 10.1021/jacs.1c00462. Epub 2021 Apr 28.
Carbapenems stand as one of the last-resort antibiotics; however, their efficacy is threatened by the rising number and rapid spread of carbapenemases. Effective antimicrobial stewardship thus calls for rapid tests for these enzymes to aid appropriate prescription and infection control. Herein, we report the first effective pan-carbapenemase reporter with a broad scope covering all three Ambler classes. Using a chemical biology approach, we demonstrated that the absence of the 1β-substituent in the carbapenem core is key to pan-carbapenemase recognition, which led to our rational design and probe development. provides a dual colorimetric-fluorogenic response upon carbapenemase-mediated hydrolysis. A clear visual readout can be obtained within 15 min when tested against a panel of carbapenemase-producing Enterobacteriaceae (CPE) clinical isolates that notably includes OXA-48 and OXA-181-producing strains. Furthermore, can be applied to the detection of carbapemenase activity in CPE-spiked urine samples.
碳青霉烯类抗生素是最后的抗生素之一；然而，它们的疗效受到碳青霉烯酶数量不断增加和迅速传播的威胁。因此，有效的抗菌药物管理需要对这些酶进行快速检测，以帮助合理用药和控制感染。在此，我们报告了首个有效的泛碳青霉烯酶报告分子，其涵盖范围广泛，包括所有三种安布勒分类。通过化学生物学方法，我们证明碳青霉烯核心中1β-取代基的缺失是泛碳青霉烯酶识别的关键，这促使我们进行合理设计并开发探针。该探针在碳青霉烯酶介导的水解作用下产生双色比色-荧光响应。当针对一组产碳青霉烯酶的肠杆菌科（CPE）临床分离株进行测试时，15分钟内即可获得清晰的视觉读数，这些分离株尤其包括产OXA-48和OXA-181的菌株。此外，该探针可用于检测加标有CPE的尿液样本中的碳青霉烯酶活性。
