Treating antibiotic-resistant infections with peptides inspired by human saliva
Treating antibiotic-resistant infections with peptides inspired by human saliva

Treating antibiotic-resistant infections with peptides inspired by human saliva

Credit: Pixabay/CC0 public domain

Antibiotic resistance is a problem that affects tens of millions of people worldwide every year. According to the CDC, “more than 2.8 million antibiotic-resistant infections occur in the United States each year, and more than 35,000 people die as a result.” Drug-resistant infections threaten advances in surgery, wound healing, cancer treatment, organ transplants, and many other areas of modern medicine by diminishing our ability to control infections.

As the nation and the world grapple with this formidable challenge, recently published work by researchers at the University of Minnesota could have a significant and positive impact on how we fight bacterial infections that are resistant to more traditional antibiotics, particularly immunocompromised people. populations. The study, recently published in PLUS ONE by co-authors Sven-Ulrik Gorr, professor in the School of Dentistry, and Elizabeth Hirsch, associate professor in the College of Pharmacy, examined an antibacterial peptide developed at the School of Dentistry and its potential impact on drug-resistant bacteria.

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The peptide is inspired by the structure of the human salivary protein, BPIFA2. The new research focused on whether the peptide could kill common resistant bacteria and bacterial biofilms, and whether the bacteria would become resistant to the new peptide.

To do this, they tested both a “left-handed” (LGL13K) and a “right-handed” version (DGL13K) of the GL13K peptide. These peptides were tested against drug-resistant Gram-negative bacteria in Hirsch’s lab.

They found:

  • Although both versions of the peptide killed common Gram-negative bacteria, those bacteria did not develop resistance to the DGL13K peptide.
  • Although the LGL13K peptide led to drug resistance in bacteria, the same resistance did not inhibit DGL13K’s ability to target these bacteria.
  • Based on these findings, the researchers concluded that peptides developed from salivary protein may be effective in fighting bacteria, including drug-resistant Gram-negative bacteria, which are difficult to kill and harder to prevent from defending against antibiotics.

“We were able to demonstrate significant in vitro activity against the multidrug-resistant bacteria tested in this project,” said Hirsch. “There are very few antibiotics on the market with activity against these organisms, particularly resistant Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii. Further investigation of this peptide in clinical development will be important for potential future treatment options.”

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Going forward, Gorr and Hirsch are exploring alternative uses for the drug, including how long drug resistance remains elusive for these bacteria. The peptide is also being tested in wound infection models in collaboration with the University’s Center for Translational Medicine and Experimental Surgical Services.

Whether the bacteria learn to fight the antimicrobial properties of the DGL13K peptide, or the bacteria never catch up, this new discovery creates a way forward for fighting hard-to-kill bacteria while providing more time to learn why these drugs work well and how we can continue to fight against bacteria and drug resistance.

“Without new antibiotics, we will see the end of modern medicine,” Gorr said.

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The collaboration between the Faculty of the School of Dental Medicine and the College of Pharmacy was essential to the success of the study.

“We provided the peptides and found expertise in drug-resistant bacteria through pharma,” Gorr said. “Dr. Hirsch brought her knowledge and I brought mine—neither of us could have done it alone. This is what university is all about.

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More information:

Sven-Ulrik Gorr et al., The antimicrobial peptide DGL13K is active against drug-resistant gram-negative bacteria, and sub-inhibitory concentrations stimulate bacterial growth without inducing resistance, PLUS ONE (2022). DOI: 10.1371/journal.pone.0273504

Provided by the University of Minnesota

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