Progress in targeting bacterial transcription.
The bacterial RNA polymerase (RNAP) is an essential enzyme that is responsible for making RNA from a DNA template and is targeted by several antibiotics. Rifampicin was the first of such antibiotics to be described and is one of the most efficient anti-tuberculosis drugs in use. In the past five years, structural studies of bacterial RNAP and the resolution of several complexes of drugs bound to RNAP subunits have revealed molecular details of the drug-binding sites and the mechanism of drug action. This knowledge opens avenues for the development of antibiotics. Here these drugs are reviewed, together with their mechanisms and their potential interest for therapeutic applications.
Villain-Guillot
Philippe
P
CNRS UMR 5236, UM1 UM2, Centre d'études d'agents pathogènes et Biotechnologies our la Santé, Av Charles Flahault, 34093 Montpellier, France.
Bastide
Lionel
L
Gualtieri
Maxime
M
Leonetti
Jean-Paul
JP
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000904:Antibiotics, Antitubercular / Q000494:pharmacology; D001665:Binding Sites / Q000235:genetics; D012321:DNA-Directed RNA Polymerases; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D021122:Protein Subunits / Q000235:genetics; D012329:RNA, Bacterial / Q000187:drug effects; D012293:Rifampin / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D000904:Antibiotics, Antitubercular; D021122:Protein Subunits; D012329:RNA, Bacterial; D012321:DNA-Directed RNA Polymerases; D012293:Rifampin