Abstract
There is great interest in the development of antimicrobial peptides as a potentially novel class of antimicrobial agents. Several structural determinants are responsible for the antimicrobial and cytolytic activity of antimicrobial peptides. In our study, a new synthetic peptide analog, AamAP1-Lysine from the naturally occurring scorpion venom antimicrobial peptide AamAP1, was designed by modifying the parent peptide in order to increase the positive charge and optimize other physico-chemical parameters involved in antimicrobial activity. AamAP1-Lysine displayed potent antibacterial activity against Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration was in the range of 5 to 15 µM with a 10 fold increase in potency over the parent peptide. The hemolytic and antiproliferative activity of AamAP1-Lysine against eukaryotic mammalian cells was minimal at the concentration range needed to inhibit bacterial growth. The antibacterial mechanism analysis indicated that AamAP1-Lysine is probably inducing bacterial cell death through membrane damage and permeabilization determined by the release of β-galactosidase enzyme from peptide treated E. coli cells. DNA binding studies revealed that AamAP1-Lysine caused complete retardation of DNA migration and could display intracellular activities in addition to the membrane permeabilization mode of action reported earlier. In conclusion, AamAP1-Lysine could prove to be a potential candidate for antimicrobial drug development in future studies.
Highlights
Antimicrobial resistance currently represents one of the biggest challenges facing human health and the medical community
The peptide sequence of the natural scorpion venom antimicrobial peptide AamAP1 was used as a platform for the development of a novel synthetic peptide analog with enhanced antimicrobial activity
The rationale used for designing the peptide analog was to increase the positive charge on the parent peptide by substituting several amino acids found on the primary sequence with lysine amino acids while relatively optimizing other physico-chemical parameters of the parent peptide that are known to influence its activity such as hydrophobicity, hydrophobic moment, and helicity
Summary
Antimicrobial resistance currently represents one of the biggest challenges facing human health and the medical community. One of the promising alternatives for conventional antibiotics is antimicrobial peptides (AMPs) as this group of molecules display potent activities against target cells, rapid killing kinetics and a broad spectrum of activity against different microbial strains [8,9,10,11]. These peptides are usually gene coded in host organisms and are expressed either constitutively or induced by various external stimuli making the selection of resistant mutants to AMPs in vitro relatively difficult [10,11]
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