Mechanism of action of Rifampin?

Case details

A 37-year-old, female develops fever, night sweat, weight loss, and a blood- tinged cough. While in the emergency room, an infectious disease specialist is consulted, she is suspected to have pulmonary tuberculosis and is immediately prescribed with a multidrug regimen that includes rifampin (Figure). Rifampin inhibits RNA transcription because it inhibits the enzyme-

A) DNA- dependent DNA polymerase

B) DNA- dependent RNA polymerase

C) RNA- dependent DNA polymerase

D) RNA- dependent RNA polymerase

E) Reverse transcriptase.

Rifampin

Figure- Rifampin is widely used as an antitubercular drug.

The correct answer is- B) DNA dependent RNA polymerase.

DNA-dependent RNA polymerase is the enzyme responsible for the polymerization of ribonucleotides into a sequence complementary to the template strand of the gene (transcription).

Rifampicin– binds with Beta subunit of prokaryotic RNA polymerase; it is an inhibitor of prokaryotic transcription initiation.  It binds only to bacterial RNA polymerase but not to eukaryotic RNA polymerases. Therefore, Rifampicin is a powerful drug for treatment of bacterial infections. It is used for the treatment of tuberculosis and leprosy.

The other important inhibitors of transcription are- Actinomycin D, Mitomycin and alpha amanitin.

Actinomycin D– Intercalates with DNA strands, it inhibits both DNA synthesis as well as RNA synthesis by blocking chain elongation. It interacts with G·C base pairs as it requires the 2-amino group of guanine for binding. Actinomycins are used as anticancer drugs.

Mitomycin– Intercalates with DNA strands, it blocks transcription, and is used as an anticancer drug.

Alpha amanitin is a molecule made from the mushroom and is a known potent inhibitor of RNA polymerase; it inhibits RNA polymerase –II at both the initiation and elongation states of transcription.

 As regards other options:

DNA- dependent DNA polymerase is required for replication of DNA.

RNA- dependent DNA polymerase is  a reverse transcriptase or telomerase. These enzymes use RNA template for DNA synthesis.

RNA- dependent RNA polymerase catalyzes the replication of RNA from RNA template. This enzyme is possessed by viruses that carry RNA as a genome.

Reverse transcriptase is RNA- dependent DNA polymerase, this enzyme is possessed by retro viruses such as Human immuno deficiency virus.

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