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New antimicrobial molecules engineered from wasp venom

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Overuse of antibiotics over decades has resulted in a hoard of antibiotic-resistant bacteria; these could be responsible for up to 10 million deaths a year by 2050 if left without intervention. As part of the desperate search for new drugs and treatments, researchers at the University of Pennsylvania (UPenn), US, have studied wasp venom – from the Korean-yellow jacket – to treat drug-resistant infections.

The researchers first had to replace part of a highly toxic peptide in the venom of the Korean yellow-jacket wasp. The peptide, known as mastoparan-L (mast-L), kills bacteria, but is also unfortunately harmful to humans. It can destroy red blood cells and trigger a life-threatening allergic reaction, or anaphylaxis, in certain people.

A new molecule called mastoparan-MO (mast-MO) was formed after replacing a section at the end of the peptide with a pentapeptide motif.According to the researchers, mast-MO appears to make the outer membranes of bacteria more porous, allowing molecules to penetrate into them easier. At the same time, mast-MO seems to summon more immune cells to the site as well.

Tested in mice infected with lethal levels of E. coli or Staphylococcus aureus, mast-MO appeared to confer significant protection – 80% of the treated animals survived, while those that received just the natural mast-L peptide were far less likely to survive. Mast-MO was also able to be safely administered at higher doses, while mast-L invoked severe side effects at the same level.

“New antibiotics are urgently needed to treat the ever-increasing number of drug-resistant infections, and venoms are an untapped source of novel potential drugs,” said Assistant Professor César de la Fuente of UPenn, a senior author of a paper on the research. “We think that venom-derived molecules such as the ones we engineered in this study are going to be a valuable source of new antibiotics.”

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