Targeting Multiple Aminoacyl-tRNA Synthetases Overcomes the Resistance Liabilities Associated with Antibacterial Inhibitors Acting on a Single Such Enzyme

• Published in: Antimicrobial agents and chemotherapy Vol. 60; no. 10; pp. 6359 - 6361
• Main Authors: Randall, Christopher P., Rasina, Dace, Jirgensons, Aigars, O'Neill, Alex J.
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.10.2016
• Subjects: Amino Acyl-tRNA Synthetases; Amino Acyl-tRNA Synthetases - antagonists & inhibitors; Anti-Bacterial Agents; Anti-Bacterial Agents - pharmacology; Boron Compounds - pharmacology; Diamines - pharmacology; Drug Resistance, Bacterial; Drug Resistance, Bacterial - drug effects; Enzyme Inhibitors; Enzyme Inhibitors - pharmacology; Mechanisms of Resistance; Microbial Sensitivity Tests; Molecular Targeted Therapy; Mupirocin - pharmacology; Mutation Rate; Staphylococcus aureus; Staphylococcus aureus - drug effects; Staphylococcus aureus - genetics; Thiophenes - pharmacology

Bacterial aminoacyl-tRNA synthetases (aaRSs) represent promising antibacterial drug targets. Unfortunately, the aaRS inhibitors that have to date reached clinical trials are subject to rapid resistance development through mutation, a phenomenon that limits their potential clinical utility. Here, we...