Abstract
Structure-based drug design was utilized to identify potent small-molecule inhibitors of proteins within the AraC family of bacterial transcription factors, which control virulence in medically important microbes. These agents represent a novel approach to fight infectious disease and may be less likely to promote resistance development. These compounds lack intrinsic antibacterial activity in vitro and were able to limit a bacterial infection in a mouse model of urinary tract infection.
MeSH terms
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Animals
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Anti-Bacterial Agents / chemical synthesis
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Anti-Bacterial Agents / chemistry*
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Anti-Bacterial Agents / therapeutic use*
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Bacterial Proteins / antagonists & inhibitors*
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Bacterial Proteins / metabolism*
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DNA / genetics
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Disease Models, Animal
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Enterobacteriaceae / drug effects
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Inhibitory Concentration 50
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Mice
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Molecular Structure
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Protein Binding
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Pseudomonas aeruginosa / drug effects
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Staphylococcus aureus / drug effects
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Structure-Activity Relationship
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Transcription Factors / antagonists & inhibitors*
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Transcription Factors / metabolism*
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Urinary Tract Infections / drug therapy
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Urinary Tract Infections / microbiology
Substances
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Anti-Bacterial Agents
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Bacterial Proteins
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Transcription Factors
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DNA