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Fluorogenic Probes with Substitutions at the 2 and 7 Positions of Cephalosporin are Highly BlaC‐Specific for Rapid Mycobacterium tuberculosis Detection
Author(s) -
Cheng Yunfeng,
Xie Hexin,
Sule Preeti,
Hassounah Hany,
Graviss Edward A.,
Kong Ying,
Cirillo Jeffrey D.,
Rao Jianghong
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201405243
Subject(s) - mycobacterium tuberculosis , cephalosporin , tuberculosis , microbiology and biotechnology , sputum , mycobacterium bovis , mycobacterium , biology , virology , chemistry , medicine , antibiotics , pathology
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.