Abstract
Antibiotics with novel mechanisms of action are desperately needed to combat the increasing rates of multidrug-resistant infections. Bacterial pantothenate kinase (PanK) has emerged as a target of interest to cut off the biosynthesis of coenzyme A. Herein we report the results of an in vitro high-throughput screen of over 10 000 small molecules against Bacillus anthracis PanK, as well as a follow-up screen of hits against PanK isolated from Pseudomonas aeruginosa and Burkholderia cenocepacia. Nine hits are structurally categorized and analyzed to set the stage for future drug development.
Keywords:
Bacillus; Pseudomonas; antibiotic resistance; high-throughput screening; pantothenate kinase.
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Anti-Bacterial Agents / chemical synthesis
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / pharmacology*
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Bacillus anthracis / drug effects*
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Bacillus anthracis / enzymology
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Dose-Response Relationship, Drug
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Microbial Sensitivity Tests
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Molecular Structure
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Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors*
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Phosphotransferases (Alcohol Group Acceptor) / metabolism
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology*
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Structure-Activity Relationship
Substances
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Anti-Bacterial Agents
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Protein Kinase Inhibitors
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Phosphotransferases (Alcohol Group Acceptor)
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pantothenate kinase