Fidaxomicin is an inhibitor of the initiation of bacterial RNA synthesis.

Article Details

Citation

Artsimovitch I, Seddon J, Sears P

Fidaxomicin is an inhibitor of the initiation of bacterial RNA synthesis.

Clin Infect Dis. 2012 Aug;55 Suppl 2:S127-31. doi: 10.1093/cid/cis358.

PubMed ID
22752861 [ View in PubMed
]
Abstract

Fidaxomicin was recently approved for the treatment of Clostridium difficile infection. It inhibits transcription by bacterial RNA polymerase. Because transcription is a multistep process, experiments were conducted in which fidaxomicin was added at different stages of transcriptional initiation to identify the blocked step. DNA footprinting experiments were also conducted to further elucidate the stage inhibited. Fidaxomicin blocks initiation only if added before the formation of the "open promoter complex," in which the template DNA strands have separated but RNA synthesis has not yet begun. Binding of fidaxomicin precludes the initial separation of DNA strands that is prerequisite to RNA synthesis. These studies show that it has a mechanism distinct from that of elongation inhibitors, such as streptolydigin, and from the transcription initiation inhibitors myxopyronin and the rifamycins.

DrugBank Data that Cites this Article

Drugs
Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
FidaxomicinRNA polymerase sigma factorProteinClostridium difficile (strain 630)
Yes
Inhibitor
Details