Fluorogenic Probes with Substitutions at the 2 and 7 Positions of Cephalosporin are Highly BlaC‐Specific for Rapid Mycobacterium tuberculosis Detection |
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| Authors: | Dr. Yunfeng Cheng Dr. Hexin Xie Dr. Preeti Sule Dr. Hany Hassounah Prof. Edward A. Graviss Prof. Ying Kong Prof. Jeffrey D. Cirillo Prof. Jianghong Rao |
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| Affiliation: | 1. Molecular Imaging Program at Stanford, Departments of Radiology and Chemistry, Stanford University, 1201 Welch Road, Stanford, CA 94305‐5484 (USA);2. Current address: Shanghai Key Laboratory of New Drug Design, East China University of Science and Technology (China);3. Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center (USA);4. Department of Pathology and Genomic Medicine, Houston Methodist Research Institute (USA);5. Department of Microbiology, Immunology, and Biochemistry, University of Tennessee (USA) |
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| Abstract: | Current methods for the detection of Mycobacterium tuberculosis (Mtb) are either time consuming or require expensive instruments and are thus are not suitable for point‐of‐care diagnosis. The design, synthesis, and evaluation of fluorogenic probes with high specificity for BlaC, a biomarker expressed by Mtb, are described. The fluorogenic probe CDG‐3 is based on cephalosporin with substitutions at the 2 and 7 positions and it demonstrates over 120 000‐fold selectivity for BlaC over TEM‐1 Bla, the most common β‐lactamase. CDG‐3 can detect 10 colony‐forming units of the attenuated Mycobacterium bovis strain BCG in human sputum in the presence of high levels of contaminating β‐lactamases expressed by other clinically prevalent bacterial strains. In a trial with 50 clinical samples, CDG‐3 detected tuberculosis with 90 % sensitivity and 73 % specificity relative to Mtb culture within one hour, thus demonstrating its potential as a low‐cost point‐of‐care test for use in resource‐limited areas. |
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| Keywords: | diagnostic tests fluorogenic probes lactams β ‐lactamases Mycobacterium tuberculosis |
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