Objectives: Despite extensive functional screening of the bacterial RNA polymerase (RNAP) over the past years, very few novel inhibitors have been reported. We have, therefore, decided to screen with a radically different, non-enzymic, protein–protein interaction assay. Our target is the highly conserved RNAP–σ interaction that is essential for transcription.
Methods: Small molecule inhibitors of the RNAP–σ interaction were tested for their activity on transcription and on bacteria.
Results: These compounds have antibacterial activity against Gram-positive bacteria including multiresistant clinical isolates.
Conclusions: This is, to our knowledge, the first example of a small molecule inhibitor of this interaction.
Keywords: transcription; antibacterial drug screening; antibacterials; antibiotic resistance; anti-infective agents
Journal Article. 4108 words. Illustrated.
Subjects: Medical Oncology ; Critical Care
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