Fluorogenic probes with substitutions at the 2 and 7 positions of cephalosporin are highly BlaC-specific for rapid mycobacterium tuberculosis detection

Yunfeng Cheng, Hexin Xie, Preeti Sule, Hany Hassounah, Edward A. Graviss, Ying Kong, Jeffrey D. Cirillo, Jianghong Rao

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)9360-9364
Number of pages5
JournalAngewandte Chemie - International Edition
Volume53
Issue number35
DOIs
StatePublished - Aug 25 2014

Keywords

  • Mycobacterium tuberculosis
  • diagnostic tests
  • fluorogenic probes
  • lactams
  • β-lactamases

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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