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Updated: Sep 12, 2025
The Use of a β-lactamase-based Conductimetric Biosensor Assay to Detect Biomolecular Interactions
Published on: February 1, 2018
SsrA-based design of BacPROTACs for β-lactamase degradation in Gram-negative bacteria
Qichang Nie1,2, Jessie Wing-Yin Wu3,4, Kun Zhang5
1Department of Biomedical Sciences, and Tung Biomedical Sciences Centre, College of Biomedicine, City University of Hong Kong, Kowloon, Hong Kong SAR, China. chiklau@cityu.edu.hk.
Abstract:
Antimicrobial resistance (AMR) challenges infection control amid limited antibiotic innovation. While bacterial proteolysis-targeting chimeras (BacPROTACs) degrade resistance factors in Gram-positive pathogens, their application in critical Gram-negative species remains unexplored. We engineered a Gram-negative-specific BacPROTAC, NacssrA-1, to degrade the β-lactamase CTX-M-14 via ClpXP. This molecule demonstrated dual-binding specificity, dose-dependent proteolysis, and cefotaxime resensitization in resistant E. coli, enabling precision AMR targeting.
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