Variations on an old drug generate promising clinical candidates for tuberculosis treatment, reports a study published this week in Nature Medicine. The work, done in mice, validates efforts to repurpose and modify existing drugs to increase their antibacterial efficacy.
Spectinomycin is a naturally found product that acts as an antibiotic, binding to bacterial ribosomes and blocking bacterial protein synthesis; however, it has only modest activity against Mycobacterium tuberculosis. Richard Lee and colleagues synthetically modified spectinomycin to create new drugs called spectinamides, which could potently inhibit M. tuberculosis growth in culture and in infected mice. These drugs selectively inhibited mycobacterial protein synthesis-sparing eukaryotic ribosomes-and avoided removal from the cell by a key drug transporter, thereby increasing mycobacterial killing activity.