Effects of Conventional Surfactants on the Activity of Designed Antimicrobial Peptide

In this article, the interaction between a designed antimicrobial peptide (AMP) G(IIKK)(3)I-NH2 (G(3)) and four typical conventional surfactants (sodium dodecyl sulfonate (SDS), hexadecyl trimethyl ammonium bromide (C(16)TAB), polyoxyethylene (23) lauryl ether (C12EO23), and tetradecyldimethylamine oxide (C(14)DMAO)) 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 G(3) conformation changed from random coil, to beta-sheet, and then to a-helix with increasing SDS concentration, showing a range of structural transformation driven by the different interactions with SDS. The antimicrobial activity of G(3) 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 G(3) and C(16)TAB, C12EO23, and C(14)DMAO were much weaker than SDS. As a result, the surface tension of surfactants with G(3) did not change much, neither did the secondary structures of G(3). The antimicrobial activities of G(3) were little affected in the presence of C12EO23, slightly improved by C(14)DMAO, and clearly enhanced by cationic surfactant C(16)TAB due to its strong cationic and antimicrobial nature, consistent with their surface physical activities as binary mixtures. Although AMP G(3) did not show activity to fungus, the mixtures of AMP/C(16)TAB and AMP/C(14)DMAO could kill C. albicans at high surfactant concentrations. The mixtures had rather high cytotoxicity to NIH 3T3 and HSF cells although G(3) 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.