Novel synthetic molecules targeting the bacterial RNA polymerase assembly.
OBJECTIVE
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.
André
Estelle
E
CPBS CNRS UMR 5160, Faculté de Pharmacie 15 Avenue Charles Flahault, BP 14491, 34093 Montpellier Cedex 5, France.
Bastide
Lionel
L
Michaux-Charachon
Sylvie
S
Gouby
Anne
A
Villain-Guillot
Philippe
P
Latouche
Jaqueline
J
Bouchet
Aurélie
A
Gualtiéri
Maxime
M
Leonetti
Jean-Paul
JP
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001408:Bacillus anthracis / Q000187:drug effects; D001409:Bacillus cereus / Q000187:drug effects; D001419:Bacteria / Q000187:drug effects* / Q000201:enzymology*; D012321:DNA-Directed RNA Polymerases / Q000187:drug effects*; D024881:Drug Resistance, Bacterial; D004797:Enzyme-Linked Immunosorbent Assay; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D047468:Immunoprecipitation; D008826:Microbial Sensitivity Tests; D013212:Staphylococcus epidermidis / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects
D000900:Anti-Bacterial Agents; D012321:DNA-Directed RNA Polymerases