Synthetic Short Cryptic Antimicrobial Peptides as Templates for the Development of Novel Biotherapeutics Against WHO Priority Pathogen

Abstract

Background

The emergence of multidrug-resistant pathogens through excessive and indiscriminate use of antibiotics, together with the lack of highly efficient treatment options for bacterial infections, has raised the development of novel antimicrobial agents to top priority. In this context, cryptic host defense peptides (cHDPs) are being explored as a novel class of antimicrobial agents. In this study, short peptides were designed from the long nonantibacterial protein ToAP2 and analysed for their positive net charge, hydrophobicity, hydrophobic moment, hydrophobic and hydrophilic planes.

Methods

From the designed fragments, five 15 amino acid fragments were synthesised by solid-phase peptide synthesis (SPPS) and analysed for antimicrobial activity against ESKAPE pathogens. All the peptides were subject to cytotoxicity, mode of action, structure and function studies to find the best template for further optimisation.

Results

Among them, two peptides, FKL15 and SKL15, showed better efficiency in killing P. aeruginosa under physiological salt and plasma conditions with no cytotoxicity issues. Further, the peptides destroyed the bacterial membranes and adopted a random coil structure in the presence of the bacteria.

Conclusions

The data indicates that FKL15 and SKL15 are promising antimicrobial peptides against antibiotic-resistant bacteria with great potential to develop as drugs with high economic value.