Fast Fluorescent Probes Detect TB

A fluorogenic probe highly specific for an enzyme produced by the tuberculosis bacterium permits detection of the pathogen at low levels in unprocessed human sputum in less than 10 minutes, scientists at Stanford University, Texas A&M University, and Global BioDiagnostics report (Nat. Chem., DOI: 10.1038/nchem.1435). Stanford’s Jianghong Rao and coworkers created a family of molecular probes that serve as substrates for the TB enzyme BlaC. The enzyme catalyzes the hydrolysis of β-lactams, including cephalosporins that aren’t susceptible to all lactamases. The probes consist of a fluorescent dye attached to a cephalosporin anchor. When BlaC hydrolyzes the probe to liberate the dye, the dye can be detected with simple equipment. The best probe (shown) is 1,000-fold more active with TB-specific BlaC than with β-lactamases common to gram-negative bacteria, which can give rise to false-positive diagnoses. “In most of the world, TB diagnosis is still done using very primitive technology,” notes Clifton E. Barry III, a TB researcher at the National Institutes of Health. “While the new probes and the technology are beautiful work, the actual utility of this in the real world is likely to be minimal for the foreseeable future.”