Peptides target key enzymes in bacterial biofilms

Peptide disrupts biofilm formation by targeting a key enzyme.

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Breakthrough peptide research is revolutionizing the field of bacterial biofilm combat. Biofilms, communities of bacteria embedded in a protective matrix, pose significant challenges in healthcare, industry, and environmental settings. Traditional antibiotics struggle to penetrate and eradicate these biofilms effectively, leading to persistent infections and treatment failures. However, recent advancements in peptide research have opened new avenues for tackling this problem.

Peptides, short chains of amino acids, exhibit remarkable antimicrobial properties and offer a promising alternative to conventional antibiotics. Through innovative studies and discoveries, scientists are uncovering novel peptide-based strategies that can disrupt and eliminate bacterial biofilms, offering hope for more effective treatments and improved outcomes.

Researchers from the University of St Andrews have made significant strides in combating bacteria growing in biofilms, a prevalent issue in up to 80% of human infections. These biofilms pose a significant challenge in infection treatment as they reduce the effectiveness of antibiotics and lead to various medical complications, such as infections associated with joint replacements, prosthetic devices, and contaminated medical equipment. More specific treatments for biofilms further complicate their management and treatment.

However, in a groundbreaking study published in Nature Chemical Biology on June 29th, a team led by Dr. Clarissa Melo Czekster and Dr. Christopher Harding from the School of Biology at St Andrew’s, in collaboration with researchers from the University of Dundee, developed antimicrobial peptides that specifically target the harmful bacteria thriving within biofilms. This innovative approach holds great promise for overcoming the challenges posed by biofilms and improving infection management.

The research team has made significant progress by investigating the functioning of a crucial enzymes, PaAP, in biofilms and introducing a groundbreaking strategy to inhibit its activity. Their potent inhibitor explicitly targets cells of the human pathogen Pseudomonas aeruginosa within biofilms. This pathogen, recognized as a top concern by the World Health Organization, is responsible for chronic infections in patients with cystic fibrosis, highlighting the urgent need for a biofilm inhibitor.

Dr. Czekster and the team collaborate with the University of St Andrews Technology Transfer Centre and industry partner Locate Bio to commercialize this technology. Locate Bio is conducting trials to explore how these peptides can be integrated with their Programmed Drug Release technology to develop innovative ortho-biologic solutions and products. The Technology Transfer Centre has also filed a UK priority patent application for this breakthrough research.

Dr. Czekster said, “Our research reveals how designed inhibitors can target a key enzyme in bacterial virulence, offering molecular insights applicable to aminopeptidases in diverse organisms. This remarkable new research presents an innovative strategy to target bacterial biofilms and pave the way for better treatment of bacterial infection.”

In conclusion, this study highlights the significance of targeting secreted aminopeptidases, such as PaAP, as a novel approach to combat P. aeruginosa biofilms. The cyclic peptide developed in this research demonstrates potent anti-biofilm activity, showing promise for addressing the urgent need for effective biofilm inhibitors. Further investigations and clinical trials are warranted to explore the therapeutic potential of this strategy in treating biofilm-associated infections caused by P. aeruginosa.

Journal Reference:

  1. Harding, C.J., Bischoff, M., Bergkessel, M. et al. An anti-biofilm cyclic peptide targets a secreted aminopeptidase from P. aeruginosa. Nature Chemical Biology. DOI: 10.1038/s41589-023-01373-8.
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