Membrane interactions and biological activity of antimicrobial peptides from Australian scorpion

Abstract

UyCT peptides are antimicrobial peptides isolated from the venom of the Australian scorpion. The activity of the UyCT peptides against Gram positive and Gram negative bacteria and red blood cells was determined. The membrane interactions of these peptides were evaluated by dye release (DR) of the fluorophore calcein from liposomes and isothermal titration calorimetry (ITC); and their secondary structure was determined by circular dichroism (CD). Three different lipid systems were used to mimic red blood cells, Escherichia coli and Staphylococcus aureus membranes. UyCT peptides exhibited broad spectrum antimicrobial activity with low MIC for S. aureus and multi-drug resistant Gram negative strains. Peptide combinations showed some synergy enhancing their potency but not hemolytic activity. The UyCT peptides adopted a helical structure in lipid environments and DR results confirmed that the mechanism of action is by disrupting the membrane. ITC data indicated that UyCT peptides preferred prokaryotic rather than eukaryotic membranes. The overall results suggest that UyCT peptides could be pharmaceutical leads for the treatment of Gram negative multiresistant bacterial infections, especially against Acinetobacter baumanni, and candidates for peptidomimetics to enhance their potency and minimize hemolysis. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova.

Orally Delivered Scorpion Antimicrobial Peptides Exhibit Activity against Pea Aphid (Acyrthosiphon pisum) and Its Bacterial Symbionts

“…The observed insecticidal and antibacterial activities of scorpion AMPs against A. pisum and its bacterial symbionts are supported by earlier research in which indolicidin, an AMP from bovine neutrophils, showed activity against the green peach aphid Myzus persicae (Sulzer) and also affected the bacteriome [ 50 ]. Furthermore, scorpion AMPs (UyCT3, UyCT5, Uy192, Um4, D11) and indolicin showed activity against Escherichia coli , which is closely related to B. aphidicola , providing further support for our observations [ 20 , 21 , 28 , 51 , 52 ].…”

“…We selected AMPs from two Australian scorpion species ( U. yaschenkoi and U. manicatus ) because the evolution of scorpions has involved the development of venom glands producing peptides and proteins that can efficiently kill insect prey [ 24 , 26 ]. Certain scorpion AMPs are also active against human pathogenic bacteria [ 21 , 28 ]. We used three insect AMPs (cecropin A, apidaecin and stomoxyn), as well as a synthetic insecticide (imidacloprid) and antibiotic (rifampicin) as controls to evaluate the scorpion AMPs.…”

“…Scorpion AMPs belong to the non-disulfide-bridged peptides (NDBP) family, which have diverse biological functions, including antimicrobial, bradykinin-potentiating, and immunomodulatory activities [ 20 , 21 , 22 , 23 ]. Scorpion AMPs have only been investigated against human pathogenic bacteria showing low minimal inhibitory concentrations (MICs), even against multi-drug-resistant bacteria [ 20 , 21 ]. However, their use as antibiotics has proven challenging due to their mildly haemolytic activity [ 19 ].…”

Utilisation of the isobole methodology to study dietary peptide–drug and peptide–peptide interactive effects on dipeptidyl peptidase IV (DPP-IV) inhibition

“…This indicates that the overall DPP-IV inhibitory effect seen in food protein hydrolysates originates from a mixture of peptides rather than a single peptide. The isobole methodology has been mainly utilised to study interactive effects between 75 drugs, fertilisers, pesticides and phytochemicals 13 with a limited number of examples applied to antimicrobial peptide mixtures 20,21 . An additive effect of Sitagliptin (when studied at one level) and peptide mixtures on DPP-IV inhibitory properties has previously been shown 11 .…”

Interaction of cationic antimicrobial peptides from Australian frogs with lipid membranes

“…Understanding the relationship between AMP structure and its mode of action and knowing the specific process for AMP action are vital for the design of new antibiotic peptides. To understand their mode of action, the interaction of AMPs have been studied with Gram‐negative Escherichia coli , Gram‐positive S. aureus and Bacillus subtilis , and human red blood cells (RBCs) in vivo and in vitro …”