Abstract
Hp1404, identified from the venom of the scorpion Heterometrus petersii, displays antimicrobial activity with cytotoxicity. Several synthetic peptides were designed based on the parent peptide Hp1404 to reduce cytotoxicity and improve activity (deletion of glycine and phenylalanine, substitution with leucine and lysine). The analogue peptides generated comprised 12 amino acids and displayed amphipathic α-helical structures, with higher hydrophobic moments and net positive charge than those of the Hp1404. The analogues showed less hemolytic and toxic effects toward mammalian cells than the Hp1404, especially Hp1404-T1e, which exhibited particularly potent antibacterial and antibiofilm activities against multidrug-resistant Pseudomonas aeruginosa (MRPA) strains. The analogue peptide Hp1404-T1e was more stable against salt and trypsin than the Hp1404. Hp1404’s mechanism of action involves binding to lipopolysaccharide (LPS), thereby killing bacteria through membrane disruption. Hp1404-T1e kills bacteria more rapidly than Hp1404 and not only seems to bind more strongly to LPS but may also be able to enter bacterial cells and interact with their DNA. Additionally, Hp1404-T1e can effectively kill bacteria in vivo. The results of this study indicate that Hp1404-T1e not only displays antimicrobial activity, but is also functional in physiological conditions, confirming its potential use as an effective therapeutic agent against MRPA.
Highlights
IntroductionAntibiotics have been widely used as therapeutic agents against infectious diseases
Since their discovery, antibiotics have been widely used as therapeutic agents against infectious diseases
As the emergence of multidrug-resistant microbes has grown into a global problem, significant research efforts are currently being channelled into the development of alternative antibiotics
Summary
Antibiotics have been widely used as therapeutic agents against infectious diseases Their indiscriminate use has led to the rapid emergence of increasingly resistant strains. AMPs can be used against a broad spectrum of pathogenic agents such as gram-negative and gram-positive bacteria, fungi, parasites, and viruses[9] They are small biological molecules consisting of 12–50 amino acid residues. AMPs have a net charge ranging from +2 to +7 owing to a surplus of basic amino acids (arginine, lysine, and histidine), and display amphipathic properties[10] Based on their secondary structure, which plays a role in determining their target-cell specificity, AMPs are classified as α-helical, β-sheet, loop, or extended[11,12]. It is not toxic to mammalian cells at concentrations below 50 μM20
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