These authors contributed equally to this work.
Fluorogenic Probes with Substitutions at the 2 and 7 Positions of Cephalosporin are Highly BlaC-Specific for Rapid Mycobacterium tuberculosis Detection†
Article first published online: 2 JUL 2014
© 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Angewandte Chemie International Edition
Volume 53, Issue 35, pages 9360–9364, August 25, 2014
How to Cite
Cheng, Y., Xie, H., Sule, P., Hassounah, H., Graviss, E. A., Kong, Y., Cirillo, J. D. and Rao, J. (2014), Fluorogenic Probes with Substitutions at the 2 and 7 Positions of Cephalosporin are Highly BlaC-Specific for Rapid Mycobacterium tuberculosis Detection. Angew. Chem. Int. Ed., 53: 9360–9364. doi: 10.1002/anie.201405243
This work was supported by grants from the Bill and Melinda Gates Foundation (grant no 48523), Global BioDiagnostics Corp. (supported by a Wellcome Trust translation award, grant no 100598) and the Center for Innovation in Global Health (CIGH) at Stanford University School of Medicine. We thank N. Ha, G. Dufour and L. Lewis for assistance in obtaining clinical samples.
- Issue published online: 21 AUG 2014
- Article first published online: 2 JUL 2014
- Manuscript Revised: 3 JUN 2014
- Manuscript Received: 13 MAY 2014
- Funded Access
- Bill and Melinda Gates Foundation. Grant Number: 48523
- Global BioDiagnostics Corp.
- Center for Innovation in Global Health (CIGH)
- diagnostic tests;
- fluorogenic probes;
- Mycobacterium tuberculosis
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.