CAMBRIDGE, Mass.—It was already known that venom from insects like bees and wasps contained compounds capable of killing bacteria, but the toxicity factor made that venom inappropriate for use as the basis of any kind of drug. However, after performing a systematic study of the antimicrobial properties of a toxin normally found in a South American wasp, researchers at the Massachusetts Institute of Technology (MIT) have now created variants of the peptide that are potent against bacteria but nontoxic to human cells.
In a study of mice, the researchers found that their strongest peptide could completely eliminate Pseudomonas aeruginosa, a strain of bacteria that causes respiratory and other infections and is resistant to most antibiotics.
“We’ve repurposed a toxic molecule into one that is a viable molecule to treat infections,” said Cesar de la Fuente-Nunez, an MIT postdoctoral researcher. “By systematically analyzing the structure and function of these peptides, we’ve been able to tune their properties and activity.”
As part of their immune defenses, many organisms—including humans—produce peptides that can kill bacteria. To help fight the emergence of antibiotic-resistant bacteria, many scientists have been trying to adapt these peptides as potential new drugs.
The peptide that de la Fuente-Nunez and his colleagues focused on in this study was isolated from a wasp known as Polybia paulista. One of the factors making the peptide attractive was its small size of only 12 amino acids.
“It’s a small enough peptide that you can try to mutate as many amino acid residues as possible to try to figure out how each building block is contributing to antimicrobial activity and toxicity,” de la Fuente-Nunez explained.
Like many other antimicrobial peptides, this venom-derived peptide is believed to kill microbes by disrupting bacterial cell membranes. The peptide has an alpha helical structure, which is known to interact strongly with cell membranes.
The researchers have begun creating additional variants that they hope will be able to clear infections at lower doses. De la Fuente-Nunez also plans to apply this approach to other types of naturally occurring antimicrobial peptides when he joins the faculty of the University of Pennsylvania next year.
“I do think some of the principles that we’ve learned here can be applicable to other similar peptides that are derived from nature,” he said. “Things like helicity and hydrophobicity are very important for a lot of these molecules, and some of the rules that we’ve learned here can definitely be extrapolated.”