Two novel antimicrobial peptides have been identified and characterized from venom of the African scorpion Pandinus imperator. The peptides, designated pandinin 1 and 2, are α-helical polycationic peptides, with pandinin 1 belonging to the group of antibacterial peptides previously described from scorpions, frogs and insects, and pandinin 2 to the group of short magainin-type helical peptides from frogs. Both peptides demonstrated high antimicrobial activity against a range of Gram-positive bacteria (2.4–5.2μM), but were less active against Gram-negative bacteria (2.4–38.2μM), and only pandinin 2 affected the yeast Candida albicans. Pandinin 2 also demonstrated strong haemolytic activity (11.1–44.5μM) against sheep erythrocytes, in contrast with pandinin 1, which was not haemolytic. CD studies and a high-resolution structure of pandinin 2 determined by NMR, showed that the two peptides are both essentially helical, but differ in their overall structure. Pandinin 2 is composed of a single α-helix with a predominantly hydrophobic N-terminal sequence, whereas pandinin 1 consists of two distinct α-helices separated by a coil region of higher flexibility. This is the first report of magainin-type polycationic antimicrobial peptides in scorpion venom. Their presence brings new insights into the mode of action of scorpion venom and also opens new avenues for the discovery of novel antibiotic molecules from arthropod venoms.
Abbreviations used: CZE, capillary zone electrophoresis; DPC, dodecylphosphocholine; Fmoc, fluoren-9-ylmethoxycarbonyl; MALDI–TOF, matrix-assisted laser-desorption ionization–time-of-flight; MIC, minimal inhibitory concentrations; Pin1, pandinin 1; Pin2, pandinin 2; RP-HPLC, reversed-phase HPLC; TFA, trifluoroacetic acid; TFE, trifluoroethanol.
Present address: Institut de Pharmacologie Moleculaire et Cellulaire, CNRS, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.
Present address: NMR Laboratory, The Walter and Eliza Hall Institute of Medical Research, 381 Royal Parade, Parkville 3052, Australia.