Regulation of the activity of an antimicrobial peptide by sterols or hopanoids: possible role in cell recognition

It is now accepted that hopanoids act as sterol-surrogates in membranes of some sterol-lacking bacteria. Here we inquiry whether the hopanoid diplopterol (DP) could attenuate the activity of the antimicrobial peptide Polybia-MP1 (MP1) similarly to cholesterol (CHO). Survival of P. aeruginosa exposed to MP1 was lower for cells incubated with DP than those incubated with CHO, and the affinity and subsequent effect of the peptide on lipid bilayers were different in the presence of DP than in the presence of CHO. Membrane properties showed a non-monotonic behavior as the peptide adsorbed, penetrated, and translocated bilayers with DP suggesting a reorganization of MP1 during these processes. We conclude that MP1 selectivity is finely tuned by lipid composition, and propose the differential interaction and consequent effect promoted by the peptide in membranes with diplopterol as a promising starting point for targeting antimicrobial peptides to hopanoid-containing bacterial membranes.