123rd General Meeting of the KCS

Type Oral Presentation
Area Oral Presentations for Young Scholars in Organic Division
Room No. Room 301+302
Time THU 09:45-10:00
Code ORGN.O-4
Subject Development of novel carbapenem-based fluorogenic probe for specific detection of carbapenemase-expressing bacteria
Authors Juhyeon Kim , Hyunah Choo1, Hak Joong Kim, Sun-Joon Min2,*
Department of Chemistry, Korea University, Korea
1center for Neuro-medicine, Korea Institute of Science and Technology, Korea
2Dept of Chemical & Molecular Eng/Applied Chemistry, Hanyang University, Korea
Abstract Carbapenem, one of the important clinically available antibiotics, is effective in treating infection of gram-negative bacteria due to its broad activity against bacterial pathogens and excellent stability against most β-lactamases. However, carbapenem-resistance enterobacteriaceaes (CREs) have been frequently observed in these days. Therefore, the burden of carbapenem resistance is increasing and becoming a major public health crisis worldwide. A primary mechanism of carbapenem resistant among the carbapenemase-producing organisms (CPOs) is including acquisition/expression of carbapenemase, which hydrolyzes the amide bond of the β-lactam ring specifically. Several cases of CREs therapeutic failure have been reported due to the poor susceptibility of carbapenemase inhibitors and rapid transmission of carbapenemase by plasmid in CREs. Accordingly, development of efficient and accurate detection method of CREs is required for infection control and guidance. Current methods for the detection of CREs can be categorized into phenotypic and genotypic methods. Although many studies have been reported on phenotypic methods that are more widely used than expensive genotypic methods, they are still time-consuming and lack sensitivity and specificity. Very recently, activity-based detection methods have been developed to overcome these disadvantages. In particular, fluorescence-based assays have attracted attention owing to relatively low cost, high sensitivity and operational simplicity. In this study, we report synthesis and evaluation of novel fluorogenic carbapenemase substrates for the specific detection of the CPOs. These probes consist of carbapenem core structure, cleavable linkers and fluorescence dyes, which can turn on fluorescence upon hydrolysis by carbapenmase. The result from clinical assessment of our new probes demonstrated that they would be applicable to practical assays to rapid and accurate detection of the CPOs for timely diagnosis and treatment of infected patients.
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