Delivering drugs with bacterial microcompartments

Brett Smith for redOrbit.com – Your Universe Online

Bacteria use microscopic compartments to separate out the various functions necessary to sustain life and researchers are currently looking for way to leverage these minuscule pockets in a range of uses, such as to deliver therapeutic drugs.

In a study set to be published the Journal of Bacteriology, researchers found that rendering these micro-compartments ineffective in salmonella led to the release of toxic metabolites that significantly damaged the bacterium.

“Microcompartments are found in hundreds of species of bacteria, in varying numbers,” said study author Thomas Bobik, a professor of molecular biology at Iowa State University, Ames. “They prevent different biochemical reactions from interfering with one-another, accelerate reactions, and sequester toxic metabolic intermediates.”

“Understanding the principles by which they function might allow us to engineer them for the production of renewable chemicals, or as containers to improve drug delivery, or perhaps identify novel target sites for antimicrobials,” Bobik added.

Salmonella can contain two different types of micro-compartments, with one type of compartment producing 1,2-propanediol and the other kind generating ethanolamine. The expression of both is prevented by genetic regulation.

However, in the new study, researchers overrode that regulation and the development of both kinds of compartments led to the toxic compounds circulating within the engineered bacteria.

“Nonfunctional micro-compartments were formed, and toxic metabolic intermediates, normally sequestered by the micro-compartment were released into the cell cytoplasm, causing cellular damage,” Bobik said.

Our cells contain storage organelle called vacuoles that are encased in a fatty lipid membrane and a protein shell. However, in salmonella, the propanediol-producing micro-compartment represses the ethanolamine-producing micro-compartment to prevent intermixing of the shell proteins of the two micro-compartments.

A happy accident

The study team said their findings indicate numerous organisms, which generate more than one type of micro-compartment, probably use an unknown mechanism to prevent negative shell protein interactions.

Bobik noted that the entire impetus of the groundbreaking discovery was an accident.

“We noticed that the inducer of the 1,2-propanediol micro-compartment repressed the ethanolamine microcompartment, when we were trying to develop a biosensor to measure vitamin B12 levels in vivo,” he said.

Almost one-fifth of bacterial genomes generate micro-compartments, and nearly 40 percent of those contain genes for multiple micro-compartments.

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