Effects of Conventional Surfactants on the Activity of Designed Antimicrobial Peptide

Abstract

In this article, the interaction between a designed antimicrobial peptide (AMP) G(IIKK)₃I-NH₂ (G₃) and four typical conventional surfactants (sodium dodecyl sulfonate (SDS), hexadecyl trimethyl ammonium bromide (C₁₆TAB), polyoxyethylene (23) lauryl ether (C₁₂EO₂₃), and tetradecyldimethylamine oxide (C₁₄DMAO)) has been studied through surface tension measurement and circular dichroism (CD) spectroscopy. The antimicrobial activities of AMP/surfactant mixtures have also been studied with Gram-negative Escherichia coli, Gram-positive Staphylococcus aureus, and the fungus Candida albicans. The cytotoxicity of the AMP/surfactant mixtures has also been assessed with NIH 3T3 and human skin fibroblast (HSF) cells. The surface tension data showed that the AMP/SDS mixture was much more surface-active than SDS alone. CD results showed that G₃ conformation changed from random coil, to β-sheet, and then to α-helix with increasing SDS concentration, showing a range of structural transformation driven by the different interactions with SDS. The antimicrobial activity of G₃ to Gram-negative and Gram-positive bacteria decreased in the presence of SDS due to the strong interaction of electrostatic attraction between the peptide and the surfactant. The interactions between G₃ and C₁₆TAB, C₁₂EO₂₃, and C₁₄DMAO were much weaker than SDS. As a result, the surface tension of surfactants with G₃ did not change much, neither did the secondary structures of G₃. The antimicrobial activities of G₃ were little affected in the presence of C₁₂EO₂₃, slightly improved by C₁₄DMAO, and clearly enhanced by cationic surfactant C₁₆TAB due to its strong cationic and antimicrobial nature, consistent with their surface physical activities as binary mixtures. Although AMP G₃ did not show activity to fungus, the mixtures of AMP/C₁₆TAB and AMP/C₁₄DMAO could kill C. albicans at high surfactant concentrations. The mixtures had rather high cytotoxicity to NIH 3T3 and HSF cells although G₃ is nontoxic to cells. Cationic AMPs can be formulated with nonionic, cationic, and zwitterionic surfactants during product development, but care must be taken when AMPs are formulated with anionic surfactants, as the strong electrostatic interaction may undermine their antimicrobial activity.