The World Health Organization estimates that 1.27 million people died directly from drug-resistant bacterial strains in 2019 and these strains contributed to 4.95 million deaths. While bacteria naturally evolve resistance to antibiotics, more strategies are needed to combat antibiotic resistance. One emerging strategy to combat antibiotic resistance is the use of antimicrobial peptides, which are chains of amino acids that function as broad-spectrum antimicrobial compounds and are key components of the innate immune system in animals, fungi, and plants. Now, a new study by researchers at the Free University of Berlin demonstrates that Pseudomonas aeruginosa was less likely to evolve antibiotic resistance when treated with a mixture of antimicrobial peptides.

The findings are published in PLOS Biology in an article titled, “The evolution of antimicrobial peptide resistance in Pseudomonas aeruginosa is severely constrained by random peptide mixtures.”

“The prevalence of antibiotic-resistant pathogens has become a major threat to public health, requiring swift initiatives for discovering new strategies to control bacterial infections,” the researchers wrote. “Hence, antibiotic stewardship and rapid diagnostics, but also the development, and prudent use, of novel effective antimicrobial agents are paramount. Ideally, these agents should be less likely to select for resistance in pathogens than currently available conventional antimicrobials. The usage of antimicrobial peptides (AMPs), key components of the innate immune response, and combination therapies, have been proposed as strategies to diminish the emergence of resistance.”

A recent GEN article highlighted antibiotic-resistant bacteria and a weakness to help overcome antibiotic resistance.

In the new study, researchers investigated whether antimicrobial peptide mixtures synthesized in the lab could reduce the risk of the pathogen P. aeruginosa from evolving antimicrobial resistance, compared to exposure to a single antimicrobial peptide. They found that using antimicrobial peptide mixtures carried a much lower risk of the bacteria developing resistance. The mixtures also helped prevent the bacteria from developing cross-resistance to other antimicrobial drugs, while maintaining—or even improving—drug sensitivity.

Overall, the findings suggest that the use of antimicrobial peptide mixtures is a strategy worth pursuing in the search for new, longer-lasting treatments for bacteria. The researchers suspect that using a cocktail of multiple antimicrobial peptides creates a larger set of challenges for bacteria to overcome, which can potentially delay the evolution of resistance, compared to traditional antibiotics. Furthermore, these cocktails can be synthesized affordably, and previous studies have shown them to be nontoxic in mice.

“Even after four weeks of exposure, a usual treatment duration for Pseudomonas infections, we could not find resistance against our new random peptide, but against other antimicrobials,” added lead author Bernardo Antunes.

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