Abstract
Antimicrobial peptides (AMPs) have been recognised as a significant therapeutic option for mitigating resistant microbial infections. It has been found recently that Plasmodium falciparum-derived, 20 residue long, peptide 35409 had antibacterial and haemolytic activity, making it an AMP having reduced selectivity, and suggesting that it should be studied more extensively for obtaining new AMPs having activity solely targeting the bacterial membrane. Peptide 35409 was thus used as template for producing short synthetic peptides (<20 residues long) and evaluating their biological activity and relevant physicochemical characteristics for therapeutic use. Four of the sixteen short peptides evaluated here had activity against E. coli without any associated haemolytic effects. The 35409-1 derivative (17 residues long) had the best therapeutic characteristics as it had high selectivity for bacterial cells, stability in the presence of human sera, activity against E. coli multiresistant clinical isolates and was shorter than the original sequence. It had a powerful membranolytic effect and low potential for inducing resistance in bacteria. This peptide’s characteristics highlighted its potential as an alternative for combating infection caused by E. coli multiresistant bacteria and/or for designing new AMPs.
Highlights
Bacterial resistance represents a serious threat to worldwide public health; pathogens resistant to currently available antibiotics are becoming more common [1]
Many studies have emphasised the need for optimising peptide sequences from early stages onward to reduce the chance of antimicrobial peptides (AMPs)’ therapeutic failure [15]
This study has presented 17 residue long peptide 35409-1 (RKKKMKKALQYIKLLKE), an improved sequence obtained from peptide 35409, which was obtained by chemical synthesis, having 86–95% chromatographic purity, truncating the N-terminal region
Summary
Bacterial resistance represents a serious threat to worldwide public health; pathogens resistant to currently available antibiotics are becoming more common [1]. Pexiganan is a magainin-derived peptide which had shown promising results in several studies for treating diabetic foot infections [23,24]; it required very high doses in an animal model to be effective and failed to demonstrate therapeutic advantages over agents available for approval by the US Food and Drug Administration (FDA) [25] Despite such disappointing results, AMPs still hold the spotlight as new generation antibiotics due to their versatility regarding being improved by chemical synthesis. This study led to the obtaining of a 17 residue long sequence having a selective membranolytic effect against E. coli cells, stable activity in the presence of human sera and low potential for inducing bacterial resistance Such characteristics suggested that peptide 35409-1 could be a candidate for combating multiresistant bacterial infections caused by E. coli and/or designing new AMPs
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