It’s easy to say that if DNA or RNA synthesis is inhibited, a cell won’t be able to get anything done at all!

So, inhibiting nucleic acid synthesis sounds like a great strategy for an antibiotic.

And luckily for us, the enzymes that carry out DNA and RNA synthesis are different enough between eukaryotic and prokaryotic cells that selective toxicity can be achieved.

• The rifamycins are a family of antibiotics that inhibit bacterial RNA polymerase.
• the antibiotic molecule is thought to bind to the polymerase in such a way that it creates a wall that prevents the chain of RNA from elongating.
• Rifamycins are bactericidal antibiotics.
• In the presence of rifamycins, bacteria can’t transcribe any genes that they need to carry out their normal functions, so they die.

Rifamycins are broad-spectrum antibiotics, meaning they’re effective against many types of bacteria, including

• Gram-negative,
• Gram-positive, and
• obligate intracellular bacteria.

There are two main reasons for this.

First, the rifamycin molecule can penetrate well into cells and tissues.

• This means that, unlike some antibiotics that can’t cross certain types of bacterial cell walls.
• The rifamycins can almost always get in and gain access to their target enzyme.

And second, enzyme’s structure is similar enough that the rifamycins can bind well to their target in diverse types of bacteria.

And how do the rifamycins achieve selective toxicity?

After all, our cells need RNA polymerases too! Luckily for us, rifamycins do not bind to eukaryotic RNA polymerases, so our own cells can continue to transcribe genes normally even when we are taking these antibiotics.

Uses

A major use of rifampin is in the treatment of mycobacterial diseases, such as tuberculosis and leprosy.

• Since mycobacteria are obligate intracellular bacteria, they live within host cells, where they’re protected against many antibiotics that can’t get inside.
• Rifamycins can penetrate well into cells and tissues, so they’re a good first choice for mycobacterial infections.

However, as with any antibiotic, there are bacteria that are resistant to the rifamycins.

The most common way for bacteria to become resistant to rifamycins is to acquire mutations that alter the structure of the RNA polymerase in such a way that rifamycins can’t bind to it as well.