Healthcare (Commonwealth Union) – As antimicrobial resistance continues to become a serious concern due to a variety of practices such as over prescription of antibiotics, the vital need for treatments becomes crucial. A wide variety of options are being considered that include CRISPR-based Therapies and nanotechnology.
A research team at the University of Alberta in Canada, has formed a potential new approach for combating antimicrobial-resistant infections, one of the most serious global health challenges today.
In a recently published study, the researchers reported preclinical findings on D-GK17, a therapeutic peptide derived from human sources.
The peptide has demonstrated stability and safety for human use, while being engineered to target the outer surfaces of bacterial and fungal cells responsible for forming biofilms. These protective layers, which can prevent antibiotics from reaching microbes effectively, are a major factor contributing to treatment resistance.
“Antimicrobial resistance is the greatest pandemic threat facing humanity, and there is an urgent need for powerful alternatives to antibiotics that bacteria cannot easily develop resistance against,” said lead researcher Dr. Prasanna Neelakantan, associate professor at the Mike Petryk School of Dentistry and Alberta Dental Association & College Chair in Oral Health Research. The research was conducted in collaboration with scientists from the University of Hong Kong and the University of Pennsylvania.
“Our peptide shredded bacterial biofilms, which cause up to 75 per cent of life-threatening infections,” said Neelakantan. “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.”
According to the World Health Organization, antimicrobial resistance was responsible for an estimated 1.27 million deaths worldwide in 2019 and was associated with an additional 4.95 million deaths.
The researchers’ therapy is derived from a human-made host defence peptide designed to offer fast, broad-spectrum activity against bacteria, viruses and fungi. However, many similar peptides become toxic at the high doses required to destroy biofilms. They are also often unstable in bodily fluids, making it difficult to develop them into effective medicines.
The Neelakantan team discovered by chance a smaller component of the human peptide LL-37, called GK17, which showed stability and low toxicity. The researchers first reported their findings three years ago.
Neelakantan indicated that GK17 met the requirements for eliminating bacteria and fungi, and it also showed potential to prevent resistance from emerging, however, it did not meet one crucial requirement — the ability to remove biofilms. He further pointed out that since biofilm destruction is essential, they created a mirror-image version of the peptide, with the hope that it would be capable of breaking down these protective structures.
The researchers tested the treatment against biofilms formed by the ESKAPE group — a collection of some of the world’s most dangerous and drug-resistant pathogens — and found that it was effective.
He indicated that very few antibiotics are capable of targeting the biofilms produced by these organisms. They wanted to determine whether our mirror-image version of GK17, known as Dextro-GK17, could both eliminate these bacteria and destroy their biofilms. The results were extremely encouraging, as it achieved both outcomes when applied topically and when delivered through injection.
Neelakantan explains that the peptide functions by disrupting the membranes of pathogen cells, forming openings that ultimately lead to cell death. He is particularly encouraged by the peptide’s ability to combat fungal infections.
Neelakantan indicated that although many research groups around the world concentrate on bacteria and viruses, their team has placed a strong emphasis on fungi because they are a major cause of illness and mortality among people with weakened immune systems. This includes individuals undergoing cancer treatment, people living with AIDS, patients receiving steroid medications, and those at the extremes of age, including infants and older adults.
