Hadrurin, a new antimicrobial peptide from the venom of the scorpion Hadrurus aztecus

A new antimicrobial peptide, hadrurin, was isolated from the venom of the M exican scorpion Hadrurus aztecus, by gel filtration on a Sephadex G-50 colu mn, followed by high performance liquid chromatography. It is a basic pepti de composed of 41 amino-acid residues with a molecular mass of 4436 Da, and contains no cysteines. A model of the three-dimensional folding of hadruri n is compatible with that of an amphipatic molecule with two or-helical seg ments. Hadrurin demonstrates antimicrobial activity at low micromolar conce ntration, inhibiting the growth of bacteria such as: Salmonella thyphi, Kle bsiella pneumoniae, Enterococcus cloacae, Pseudomonas aeruginosa, Escherich ia coli and Serratia marscences. It also shows cytolytic activity when test ed in human erythrocytes. Hadrurin and two analogs (C-terminal amidated, an d all D-enantiomer) were chemically synthesized. They were used to study th e possible molecular mechanism of action by testing their ability to dissip ate the diffusion potential of liposomes of different compositions. The res ults obtained indicate that there are no specific receptor molecules for th e action of hadrurin, and the most probable mechanism is through a membrane destabilization activity. It is surmised that hadrurin is used by the scor pion as both an attack and defense element against its prey and putative in vasive microorganisms. It is a unique peptide among all known antimicrobial peptides described, only partially similar to the N-terminal segment of ga egurin 4 and brevinin 2e, isolated from frog skin. It would certainly be a model molecule for studying new antibiotic activities and peptide-lipid int eractions.