title: Novel gramicidin formulations in cationic lipid as broad-spectrum microbicidal agents.
abstract: Dioctadecyldimethylammonium bromide (DODAB) is an antimicrobial lipid that can be dispersed as large closed bilayers (LV) or bilayer disks (BF). Gramicidin (Gr) is an antimicrobial peptide assembling as channels in membranes and increasing their permeability towards cations. In mammalian cells, DODAB and Gr have the drawbacks of Gram-positive resistance and high toxicity, respectively. In this study, DODAB bilayers incorporating Gr showed good antimicrobial activity and low toxicity. Techniques employed were spectroscopy, photon correlation spectroscopy for sizing and evaluation of the surface potential at the shear plane, turbidimetric detection of dissipation of osmotic gradients in LV/Gr, determination of bacterial cell lysis, and counting of colony-forming units. There was quantitative incorporation of Gr and development of functional channels in LV. Gr increased the bilayer charge density in LV but did not affect the BF charge density, with localization of Gr at the BF borders. DODAB/Gr formulations substantially reduce Gr toxicity against eukaryotic cells and advantageously broaden the antimicrobial activity spectrum, effectively killing Escherichia coli and Staphylococcus aureus bacteria with occurrence of cell lysis.
authors: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.
authors: Danielle A M T
authors: DA
authors: Ragioto
authors: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.
authors: Letícia D M
authors: LD
authors: Carrasco
authors: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.
authors: Ana M
authors: AM
authors: Carmona-Ribeiro
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology; D002412:Cations / Q000737:chemistry* / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D006096:Gramicidin / Q000737:chemistry* / Q000494:pharmacology; D050296:Microbial Viability / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D002412:Cations; D000644:Quaternary Ammonium Compounds; D006096:Gramicidin; C015831:dimethyldioctadecylammonium
keywords: antimicrobial peptides; bilayer fragments; cationic bilayers; dioctadecyldimethylammonium bromide; gramicidin A; self-assembly