Mucroporin, the First Cationic Host Defense Peptide from the Venom ofLychas mucronatus

Abstract

The misuse of antibiotics has led our age to a dangerous edge, as antibiotic-resistant pathogens appear to evolve more quickly than antibiotics are invented. Thus, new agents to treat bacterial infection are badly needed. Cationic host defense peptides are on the first line of a host defense system and are thought to be good candidates for treating bacterial infection. Here, a novel cationic host defense peptide, mucroporin, was cloned and characterized from the venom of Lychas mucronatus. The MIC for Staphylococcus aureus was 25 g/ml, including antibiotic-resistant pathogens. Based on the molecular template of mucroporin, mucroporin-M1 was designed by amino acid substitution. The MIC for S. aureus was 5 g/ml, including the antibiotic-resistant pathogens methicillin-resistant S. aureus, methicillin-resistant coagulase-negative Staphylococcus, penicillinresistant S. aureus, and penicillin-resistant S. epidermidis. Moreover, mucroporin-M1 also inhibited gramnegative bacteria. The modes of action of mucroporin and mucroporin-M1 were both rapid killing by disrupting the cell membrane of bacteria, and the number of surviving bacteria was reduced by about 4 to 5 orders of magnitude immediately after peptide delivery. These results showed that mucroporin could be considered a potential anti-infective drug, especially for treating antibiotic-resistant pathogens.

Ctriporin, a New Anti-Methicillin-Resistant Staphylococcus aureus Peptide from the Venom of the Scorpion Chaerilus tricostatus

“…Ctriporin was the first antimicrobial peptide found in this scorpion. It consists of 19 amino acids with a net positive charge of 2, and the amino acid sequence has about 36.8 to 47% similarity to the sequences of BmKb2 (32), imcroporin (53), and mucroporin (13), while the MIC of ctriporin peptide against S. aureus is 5 g/ml, which was about 3-to 5-fold lower than those of BmKb2, imcroporin, and mucroporin. Moreover, the MIC against MRSA was even 5-to 10-fold lower.…”

“…It has long been widely believed that scorpion venom is a mixture of natural bioactive substances (35). At present, some antimicrobial peptides have been found in scorpion venom and hemolymph (8,20), such as hadrurin (47), scorpine (11), opistoporins, parabutoporin (33), IsCTs (14), pandinins (12), mucroporin (13), imcroporin (53), and StCT1 (51), indicating that scorpion venom is also a rich resource of crude antimicrobial peptides.…”

Imcroporin, a New Cationic Antimicrobial Peptide from the Venom of the Scorpion Isometrus maculates

“…The in vivo activity of imcroporin was evaluated by determining the LD 50 of S. aureus in a mouse model. The LD 50 of S. aureus for mice was 6.8 ϫ 10 5 CFU/ml, calculated by the method of Dai et al (12). The infective dose of bacteria was about 10 times the LD 50 , so we chose the optimal infective dose for mice of about 5 ϫ 10 6 CFU/ml.…”

“…Several cationic antimicrobial peptides have been found in scorpion hemolymph and venom (9,15), including hadrurin (35), scorpine (10), opistoporins (30), parabutoporin (30), IsCTs (13,28), pandinins (11), and mucroporin (12). In the present study, we isolated a cationic antimicrobial peptide, termed imcroporin, from the cDNA library of the venomous gland of the scorpion Isometrus maculates.…”

Purificación parcial de péptidos y actividad citotóxica del veneno T. macrochirus

“…2003. p. 381-5), que poseen características farmacológicas, fisiológicas y bioquímicas, las cuales se han determinado y caracterizado estructural y funcionalmente mediante técnicas bioquímicas, como la cromatografía de exclusión (filtración en gel) (1), el intercambio iónico (2) y la cromatografía de alta resolución (HPLC), entre otras (3,4). La determinación de la secuencia de aminoácidos se hace mediante la degradación de Edman o la espectrometría de masas (5); otras técnicas incluyen ensayos de clonación molecular (6)(7)(8).…”