Abstract
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.
Copyright © 2016, American Society for Microbiology. All Rights Reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acyl-tRNA Synthetases / antagonists & inhibitors*
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Anti-Bacterial Agents / pharmacology*
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Boron Compounds / pharmacology
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Diamines / pharmacology
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Drug Resistance, Bacterial / drug effects*
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Enzyme Inhibitors / pharmacology*
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Microbial Sensitivity Tests
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Molecular Targeted Therapy
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Mupirocin / pharmacology
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Mutation Rate
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Staphylococcus aureus / drug effects*
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Staphylococcus aureus / genetics
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Thiophenes / pharmacology
Substances
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3-(aminomethyl)-7-(3-hydroxypropoxy)-1-hydroxy-1,3-dihydro-2,1-benzoxaborole
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Anti-Bacterial Agents
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Boron Compounds
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Diamines
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Enzyme Inhibitors
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REP8839
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Thiophenes
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Mupirocin
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Amino Acyl-tRNA Synthetases