A University of Alberta research team has designed a promising alternative for treating antimicrobial-resistant infections, a pressing global health issue. In a paper recently published in Cell Biomaterials, the team describes preclinical testing results for its human-derived peptide treatment, D-GK17. The peptide is stable and nontoxic to humans and is synthesized to attack the surfaces of bacterial or fungal cells that create biofilms, a sticky matrix that is often impenetrable to antibiotic treatments.

"Antimicrobial resistance is the biggest pandemic threatening humanity, so we really need potent antibiotic alternatives to which bacteria are unable to develop resistance," says principal investigator Dr. Prasanna Neelakantan, associate professor in the Mike Petryk School of Dentistry and Alberta Dental Association & College Chair in Oral Health Research, who did the work with collaborators at the University of Hong Kong and the University of Pennsylvania.

"Our peptide shredded bacterial biofilms, which cause up to 75% of life-threatening infections," Neelakantan explains. "We used skin infection models to show how our antibiotic alternative not only rescues from devastating bacterial infections, but also reduces inflammation and promotes wound healing."

Antimicrobial resistance is estimated to have directly caused 1.27 million deaths and contributed to 4.95 million deaths in 2019, according to the World Health Organization.

The team's treatment is based on a human-produced host defense peptide that provides rapid, broad-spectrum protection against bacteria, viruses and fungi. Most such peptides are toxic in the high concentrations needed to eradicate biofilms, and more importantly, they are unstable in body fluids, so it has been hard to harness their power as drugs.

The team serendipitously discovered a small subunit of the human peptide LL-37 known as GK17 that is stable and nontoxic, first publishing its findings three years ago.

"It checked the box for killing bacteria and fungi. It checked the box for preventing the development of resistance. But one box that it did not check was whether it could eradicate biofilms, which would be critical. So, we made a mirror version of our peptide, hoping it would break down biofilms," Neelakantan says.

They tested it against the biofilms created by the so-called ESKAPE group of the world's most critical pathogens, and it worked.