TY - JOUR
T1 - Fluorogenic probes with substitutions at the 2 and 7 positions of cephalosporin are highly BlaC-specific for rapid mycobacterium tuberculosis detection
AU - Cheng, Yunfeng
AU - Xie, Hexin
AU - Sule, Preeti
AU - Hassounah, Hany
AU - Graviss, Edward A.
AU - Kong, Ying
AU - Cirillo, Jeffrey D.
AU - Rao, Jianghong
PY - 2014/8/25
Y1 - 2014/8/25
N2 - 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 7positions 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. TB or not TB? A fluorogenic probe (CDG-3) was developed for BlaC, a biomarker expressed by Mycobacterium tuberculosis (Mtb). CDG-3 is based on cephalosporin with substitutions at both the 2 and 7positions and it demonstrates over 120 000-fold selectivity for BlaC over the common β-lactamase TEM-1 Bla. This rapid, low cost, sensitive, and selective method shows great potential for point-of-care tuberculosis (TB) testing in resource-limited settings.
AB - 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 7positions 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. TB or not TB? A fluorogenic probe (CDG-3) was developed for BlaC, a biomarker expressed by Mycobacterium tuberculosis (Mtb). CDG-3 is based on cephalosporin with substitutions at both the 2 and 7positions and it demonstrates over 120 000-fold selectivity for BlaC over the common β-lactamase TEM-1 Bla. This rapid, low cost, sensitive, and selective method shows great potential for point-of-care tuberculosis (TB) testing in resource-limited settings.
KW - Mycobacterium tuberculosis
KW - diagnostic tests
KW - fluorogenic probes
KW - lactams
KW - β-lactamases
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U2 - 10.1002/anie.201405243
DO - 10.1002/anie.201405243
M3 - Article
C2 - 24989449
AN - SCOPUS:84915776545
SN - 1433-7851
VL - 53
SP - 9360
EP - 9364
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 35
ER -