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Antimicrobial Agents and Chemotherapy, April 2005, p. 1340-1345, Vol. 49, No. 4
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.4.1340-1345.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Bactericidal and Antiendotoxic Properties of Short Cationic Peptides Derived from a Snake Venom Lys49 Phospholipase A2

Carlos Santamaría,1,2 Silda Larios,3 Steve Quirós,1 Javier Pizarro-Cerda,4 Jean-Pierre Gorvel,5 Bruno Lomonte,1* and Edgardo Moreno2

Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José,1 Programa de Investigación en Enfermedades Tropicales, Escuela de Medicina Veterinaria, Universidad Nacional, Heredia, Costa Rica,2 Departamento de Microbiología, Escuela de Medicina, Universidad Nacional Autónoma de Managua, León, Nicaragua,3 Institut Pasteur, Paris,4 Centre d'Immunologie de Marseille-Luminy, Marseille, France5

Received 30 June 2004/ Returned for modification 8 September 2004/ Accepted 23 November 2004

The activities of short synthetic, nonhemolytic peptides derived from the C-terminal region of myotoxin II, a catalytically inactive phospholipase A2 homologue present in the venom of the snake Bothrops asper, have been shown to reproduce the bactericidal activity of the parent protein. They combine cationic and hydrophobic-aromatic amino acids, thus functionally resembling the antimicrobial peptides of innate defenses. This study evaluated the antimicrobial and antiendotoxic properties of a 13-mer derivative peptide of the C-terminal sequence from positions 115 to 129 of myotoxin II, named pEM-2. This peptide (KKWRWWLKALAKK) showed bactericidal activity against both gram-positive and gram-negative bacteria. In comparison to previously described peptide variants derived from myotoxin II, the toxicity of pEM-2 toward eukaryotic cells in culture was significantly reduced, being similar to that of lactoferricin B but lower than that of polymyxin B. The all-D enantiomer of pEM-2 [pEM-2 (D)] retained the same bactericidal potency of its L-enantiomeric counterpart, but it showed an enhanced ability to counteract the lethal activity of an intraperitoneal lipopolysaccharide challenge in mice, which correlated with a significant reduction of the serum tumor necrosis factor alpha levels triggered by this endotoxin. Lethality induced by intraperitoneal infection of mice with Escherichia coli or Salmonella enterica serovar Typhimurium was reduced by the administration of pEM-2 (D). These results demonstrate that phospholipase A2-derived peptides may have the potential to counteract microbial infections and encourage further evaluations of their actions in vivo.

* Corresponding author. Mailing address: Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José 2060, Costa Rica. Phone: (506) 229-0344. Fax: (506) 292-0485. E-mail: blomonte{at}cariari.ucr.ac.cr.

Antimicrobial Agents and Chemotherapy, April 2005, p. 1340-1345, Vol. 49, No. 4
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.4.1340-1345.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





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