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Wasp toxin inspires new antibiotic that overcomes tough-to-treat sepsis in mice

The sting from a Korean yellow-jacket wasp doesn’t pose much of a danger to people—but it could be toxic enough to kill lethal bacteria that have become resistant to antibiotics. Now the insect has inspired scientists at the University of Pennsylvania’s Perelman School of Medicine to take a new approach to developing antibiotics.

The team started with one ingredient in the wasp’s venom, a peptide called mastoparan-L (mast-L). This protein can kill bacteria, but it wouldn’t be safe for people at high doses. So the researchers engineered a version of the protein so that it targets E. coli while leaving healthy cells alone. They described the compound in the journal Proceedings of the National Academy of Sciences.

To figure out how to alter mast-L, the scientists searched a database of known antimicrobial compounds and identified a feature that corresponded with a strong ability to kill bacteria. They took a motif inspired by that feature and used it to replace of a region of mast-L that's associated with high toxicity, calling the new compound mast-MO.

The Penn team went on to test mast-MO in mouse models of sepsis caused by E. coli. The peptide worked in 80% of the animals, they reported. They treated a second group with mast-L and found a lower survival rate and toxic side effects.

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