Krishnamoorthy Sankarganesh, Steiger Andrea K, Nelson William C, Egbert Robert G, Wright Aaron T
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, 99352, USA.
The Gene and Linda Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman, Washington, 99163, USA.
Chem Commun (Camb). 2022 Jul 19;58(58):8113-8116. doi: 10.1039/d2cc01517j.
Development of profiling strategies to provide high resolution understanding of enzymes involved in bacterial infections remains an important need. These strategies help resolve enzyme mechanisms of actions and can guide therapeutic development. We have developed a selective new activity-based probe (ABP) targeting a highly conserved surface bound enzyme, C5a peptidase, present in several pathogenic . We demonstrate our probe inhibits C5a peptidase activity and enables detection of C5a peptidase expressing pathogens in microbial mixtures. Our profiling strategy selectively labels the pathogen by phenotype and enables specific isolation of the live bacteria providing a route for further in-depth investigation. This study paves the way towards a rapid detection, isolation, and characterization pipeline for existing and emerging strains of most common pathogenic .
开发能够深入解析参与细菌感染的酶的分析策略仍然具有重要意义。这些策略有助于阐明酶的作用机制，并能指导治疗药物的研发。我们开发了一种新型选择性基于活性的探针（ABP），它靶向几种病原体中存在的一种高度保守的表面结合酶——C5a肽酶。我们证明，我们的探针能够抑制C5a肽酶的活性，并能在微生物混合物中检测出表达C5a肽酶的病原体。我们的分析策略通过表型选择性地标记病原体，并能特异性地分离活细菌，为进一步深入研究提供了途径。这项研究为快速检测、分离和鉴定最常见病原体的现有和新出现菌株的流程铺平了道路。
