Could an anti-epileptic drug provide new antibiotics?
Lamotrigine — a drug used to treat epilepsy — can stop bacteria from building the molecular machinery they need to make proteins.
Inside cells, molecular machines called ribosomes make proteins from instructions that are provided by genes. The ribosomes themselves are made up of about 50 proteins and three RNA molecules that need to be assembled like a 3-D jigsaw. In bacteria, a group of proteins called “ribosome biogenesis factors” help to assemble these pieces correctly.
To study how a biological process works, scientists often look at what happens when a component is missing or not working properly. However, this approach cannot be used to study how ribosomes are made because stopping protein production entirely will kill the cell. Another approach is to use chemicals to temporarily stop or slow down a biological process, but researchers are yet to find a chemical that can do this for ribosome assembly.
To address this problem, Jonathan Stokes and colleagues ‘screened’ 30,000 chemicals in an effort to find one or more that could affect ribosome assembly in bacteria. The screen revealed that a drug called lamotrigine — which is used to treat epilepsy and other conditions in humans — could stop the assembly of ribosomes, but did not affect the production of proteins by completed ribosomes.
The experiments also suggest that “initiation factor 2”, a protein that is involved in the production of other proteins, may also have a role in ribosome assembly. Another recent study found that the equivalent of initiation factor 2 in yeast acts as a quality control checkpoint during ribosome assembly, so the bacterial version may also perform a similar role.
It is also be possible that lamotrigine might be used to help develop a novel mechanistic class of antibiotics.
To find out more
Read the eLife research paper on which this story is based: “Discovery of a small molecule that inhibits bacterial ribosome biogenesis” (September 18, 2014).
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