Chemical probe design strategies to detect carbapenemase-producing organisms

Abstract

β-Lactam antibiotics, including carbapenems, are vital for treating bacterial infections by inhibiting cell wall synthesis. As last-resort agents against multidrug-resistant (MDR) bacteria, carbapenems are increasingly compromised by the emergence of carbapenemase enzymes, which inactivate them by hydrolyzing their β-lactam ring. Early detection of carbapenemase-producing organisms (CPOs) is therefore crucial to mitigate this growing threat. In this review, we highlight the mechanistic design principles of chemical probes that have been developed and continually refined to enhance stability, sensitivity, and specificity of carbapenemase detection. Key innovations include structural modifications to probe components-such as cores and linkers-as well as the incorporation of new fluorogenic and chemiluminescent reporters, along with a proposed strategy involving redox-activatable reporters to enhance detection accuracy and minimize false positives. These advances have facilitated the creation of rapid, visual biosensors for clinical diagnostics, enabling timely identification of resistance and guiding effective treatment. Early and precise detection of CPOs is essential to improve patient outcomes, optimize antibiotic use, and combat the global challenge of antibiotic resistance.

Keywords: Antimicrobial resistance; Carbapenemase-producing organisms; Carbapenemases; Carbapenems; Chemical probes; Diagnostics; β-Lactams.