Effect Of Antibacterial Peptide Indolicidin On The Membrane Permeability: Carrier Mechanism Versus Pore Formation

It is generally accepted that the predominant mechanism of action of antimicrobial peptides is the permeabilizaiton of bacterial membranes via formation of aqueous pores. It has been shown in the present work that the main mechanism of carboxyfluorescein (CF) leakage from lipid vesicles induced by antimicrobial peptide indolicidin is not pore formation but rather translocation across the membrane of the complexes of the dye and the peptide, i.e. indolicidin functions as a carrier of organic anions. This conclusion was made after observation of strong inhibition of CF leakage by other organic anions (such as fatty acids) and also inability of indolicidin to induce leakage of glucose and positively-charged doxorubicin. Besides, formation of complexes of indolicidin with pyrenebutanic acid was directly observed by fluorescent assay. The mode of action proposed here for indolicidin can be related to that previously postulated for oligoarginine derivatives which are able to transport organic anions across liposomal and bulk phase membranes [Sakai N. et al., ChemBioChem. 2005, 6:114-122]. The newly identified mechanism may be involved in bactericidal action of indolicidin either directly or indirectly through induction of leakage of important anionic metabolites leading to regulatory disfunction.