The antimicrobial peptide Polybia-MP1 differentiates membranes with the hopanoid, diplopterol from those with cholesterol

ALVARES, DAYANE S.; MONTI, MARIELA R.; RUGGIERO NETO, JOÃO; WILKE, NATALIA

BBA Advances

Elsevier

Año: 2021 vol. 1 p. 1 - 11

2667-1603

Polybia-MP1 is an antimicrobial peptide that shows a decreased activity in membranes with cholesterol (CHO). Since it is now accepted that hopanoids act as sterol-surrogates in some sterol-lacking bacteria, we here inquire about the impact of Polybia-MP1 on membranes containing the hopanoid diplopterol (DP) in comparison to mem- branes with CHO. We found that, despite the properties induced on lipid membranes by DP are similar to those induced by CHO, the effect of Polybia-MP1 on membranes with CHO or DP was significantly different. DP did not prevent dye release from LUVs, nor the insertion of Polybia-MP1 into monolayers, and peptide-membrane affin- ity was higher for those with DP than with CHO. Zeta potentials ( 𝜁) for DP-containing LUVs showed a complex behavior at increasing peptide concentration. The effect of the peptide on membrane elasticity, investigated by nanotube retraction experiments, showed that peptide addition softened all membrane compositions, but mem- branes with DP got stiffer at long times. Considering this, and the 𝜁results, we propose that peptides accumulate at the interface adopting different arrangements, leading to a non-monotonic behavior. Possible correlations with cell membranes were inquired testing the antimicrobial activity of Polybia-MP1 against hopanoid-lacking bac- teria pre-incubated with DP or CHO. The fraction of surviving cells was lower in cultures incubated with DP compared to those incubated with CHO. We propose that the higher activity of Polybia-MP1 against some bac- teria compared to mammalian cells is not only related to membrane electrostatics, but also the composition of neutral lipids, particularly the hopanoids, could be important.