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-sigma interaction that is essential for transcription.
Methods: Small molecule inhibitors of the RNAP-sigma 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.