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

Antimicrobial Agents and Chemotherapy 2016
C. P. Randall, Dace Rasiņa, Aigars Jirgensons, A. J. O`neill

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 confirm the intuitively correct idea that simultaneous targeting of two different aaRS enzymes prevents the emergence of spontaneous bacterial resistance at high frequency, a finding that supports the development of multitargeted anti-aaRS therapies.

DOI
10.1128/AAC.00674-16
Hyperlink
http://aac.asm.org/content/60/10/6359

Randall, C., Rasiņa, D., Jirgensons, A., O`Neill, A. Targeting Multiple Aminoacyl-tRNA Synthetases Overcomes the Resistance Liabilities Associated with Antibacterial Inhibitors Acting on a Single Such Enzyme. Antimicrobial Agents and Chemotherapy, 2016, Vol.60, pp.6359-6361. ISSN 0066-4804. Available from: doi:10.1128/AAC.00674-16

Publication language
English (en)