Chemiluminescence Detection of Hydrogen Sulfide Release by beta-Lactamase-Catalyzed beta-Lactam Biodegradation: Unprecedented Pathway for Monitoring beta-Lactam Antibiotic Bacterial Resistance

摘要

beta-Lactamase positive bacteria represent a growing threat to human health because of their resistance to commonly used antibiotics. Therefore, development of new diagnostic methods for identification of beta-lactamase positive bacteria is of high importance for monitoring the spread of antibiotic-resistant bacteria. Here, we report the discovery of a new biodegradation metabolite (H2S), generated through beta-lactamase-catalyzed hydrolysis of beta-lactam antibiotics. This discovery directed us to develop a distinct molecular technique for monitoring bacterial antibiotic resistance. The technique is based on a highly efficient chemiluminescence probe, designed for detection of the metabolite, hydrogen sulfide, that is released upon biodegradation of beta-lactam by beta-lactamases. Such an assay can directly indicate if antibiotic bacterial resistance exists for a certain examined beta-lactam. The assay was successfully demonstrated for five different beta-lactam antibiotics and eight beta-lactam resistant bacterial strains. Importantly, in a functional bacterial assay, our chemiluminescence probe was able to clearly distinguish between a beta-lactam resistant bacterial strain and a sensitive one. As far as we know, there is no previous documentation for such a biodegradation pathway of beta-lactam antibiotics. Bearing in mind the data obtained in this study, we propose that hydrogen sulfide should be considered as an emerging beta-lactam metabolite for detection of bacterial resistance.