ULTRA SHORT SELF-ASSEMBLING PEPTIDES AS BROAD SPECTRUM ANTIMICROBIAL AGENTS

The emergence of multidrug resistance in pathogens such as Staphylococcus aureus is an increasingly serious medical problem. Antibiotic resistant bacteria cause increased number of deaths each year and finding new therapeutic agents is therefore one of the greatest challenges of our era.

Antimicrobial peptides may serve as a possible solution to this challenge. These compounds are produced by a wide variety of organisms, including bacteria, fungi, insects and mammals. They have been shown to effectively target many types of both Gram negative and positive bacteria. They carry a net positive charge and are comprised of hydrophilic and hydrophobic amino acids. These attributes allow for membrane permeation and a distinct mode of action to which it is more difficult to acquire resistant against as compared to traditional antibiotic treatment.

It has recently been demonstrated that antimicrobial peptides can form amyloid-like structures and that classical amyloidogenic proteins and peptides have antimicrobial capabilities. Given these structural and functional similarities as well as the fact that some common membrane interaction mechanisms are shared by both classes of peptides, we set out to evaluate the underlining interplay between them. We developed a novel ultra-short amyloid-forming peptide with significant antimicrobial capabilities towards Escherichia coli. These experiments served as a proof-of-concept and we set out to further evaluate the broad spectrum propensity of the novel ultra-short antimicrobial peptides.

In this study, we evaluated the growth inhibition mediated by our ultra-short peptide on various bacteria, including Staphylococcus aureus, Pseudomonas aureguinosa, Enterococcus faecalis and Acinetobacter calcoaceticus A2. The newly developed novel antimicrobial peptides may provide a possible solution for the growing number of multidrug resistance cases.