Novel synthetic molecules targeting the bacterial RNA polymerase assembly

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.