Dermaseptin DA4, although closely related to dermaseptin B2, presents chemotactic and Gram-negative selective bactericidal activities.
Antimicrobial peptides participate in innate host defense by directly eliminating pathogens as a result of their ability to damage the microbial membrane and by providing danger signals that will recruit innate immune cells to the site of infection. Dermaseptin DA4 (DRS-DA4), a new antimicrobial peptide of the dermaseptin superfamily, was identified based on its chemotactic properties, contrasting with the currently used microbicidal properties assessment. The peptide was isolated and purified by size exclusion HPLC and RP-HPLC from the skin of the Mexican frog, Pachymedusa dacnicolor. MS and amino acid sequence analyses were consistent with the structure GMWSKIKNAGKAAKAAAKAAGKAALGAVSEAM. CD experiments showed that, unlike most antimicrobial peptides of the dermaseptin superfamily, DRS-DA4 is not structured in the presence of zwitterionic lipids. DRS-DA4 is a potent chemoattractant for human leukocytes and is devoid of hemolytic activity; in addition, bactericidal tests and membrane perturbation assays on model membranes and on Escherichia coli and Staphylococcus aureus strains have shown that the antibacterial effects of DRS-DA4 and permeabilization of the inner membrane are exclusively selective for Gram-negative bacteria. Interestingly, despite high sequence homology with dermaseptin S4, dermaseptin B2 was not able to induce directional migration of leukocytes, and displayed a broader bactericidal spectrum. A detailed structure-function analysis of closely related peptides with different capabilities, such as DRS-DA4 and dermaseptin B2, is critical for the design of new molecules with specific attributes to modulate immunity and/or act as microbicidal agents.
Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnologia, Universidad Nacional Autónoma de México, Col Chamilpa, Cuernavaca, Morelos, Mexico.
Constance
C
Auvynet
Pierre
P
Joanne
Julie
J
Bourdais
Pierre
P
Nicolas
Claire
C
Lacombe
Yvonne
Y
Rosenstein
D000595:Amino Acid Sequence; D029845:Amphibian Proteins / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D001001:Anura / Q000378:metabolism; D002630:Chemotactic Factors / Q000494:pharmacology*; D002942:Circular Dichroism; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000378:metabolism
D029845:Amphibian Proteins; D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D002630:Chemotactic Factors; D043562:Receptors, G-Protein-Coupled; C070905:dermaseptin