Antibiotic resistance isn’t just a hospital problem—it’s a growing threat on the farm, too. From poultry barns to dairy sheds, the overuse of antibiotics in agriculture has given rise to “superbugs” that endanger animals, crops, and even human health. But what if the solution has been buzzing and hopping around us all along?

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In a new study led by Bar Maron, a joint PhD student, in collaboration with Prof. Jonathan Friedman and Prof. Zvi Hayouka from the Faculty of Agriculture, Food and Environment at the Hebrew University of Jerusalem, scientists have discovered that antimicrobial peptides (AMPs)—tiny proteins that are part of the immune system of almost all organisms—can work together to block the development of bacterial resistance.

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“Bacteria are smart. When you hit them with one weapon, they often find a way around it,” says Prof. Hayouka. “But when we used two peptides at once, it was like closing all the escape routes.”

Three AMPs

The research, published in iScience, focused on Staphylococcus aureus, a significant pathogen responsible for persistent infections in animals and humans alike. Using three AMPs—melittin (from bees), temporin (from frogs), and pexiganan (a synthetic peptide inspired by nature)—the team watched how bacteria evolved over time. The results were significant: when bacteria were exposed to a single peptide, they quickly developed resistance through genetic mutations. But when two peptides were combined? The bacteria were stumped, mutating less and staying vulnerable.

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Source: Bar Maron, The Hebrew University of Jerusalem, the figure created with Biorender.com

The figure illustrates a key strategy to prevent the evolution of antimicrobial resistance. When bacteria are treated with a single antimicrobial peptide (AMP)—from a source like a honeybee (top) or a frog (bottom)—they can rapidly evolve resistance, which renders the treatment ineffective. However, when the bacteria are treated with a combination of different AMPs, they are effectively killed (center), and their ability to evolve resistance is significantly hindered. This approach makes peptide combinations a promising strategy for developing more durable, ‘resistance-proof’ therapies.

This could be an important advancement for agriculture, where antibiotic resistance has already begun to affect livestock health and farmer livelihoods. By reducing reliance on synthetic antibiotics and turning to natural peptide combinations, the industry could move toward safer, more sustainable ways of managing disease.

“These peptides are part of nature’s own defense system. Animals have been using them for millions of years,” says Prof. Friedman. “By borrowing from nature and using them wisely, we can tip the scales back in our favor.”

Hope for herd health

The findings could pave the way for new feed additives or topical treatments that keep infections in check without triggering resistance. It also offers hope for maintaining herd health without contributing to the global AMR (antimicrobial resistance) crisis.

Of course, more research is needed before these peptides make their way into farm protocols. But the message is clear: when it comes to fighting superbugs, sometimes two peptides are better than one.

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