Interaction of antimicrobial peptides with bacterial membranes

VARGAS VELEZ LEIDY STEFANIA,; N. WILKE. .

Rosario

Congreso; Reunión Anual SAB. Rosario; 2022

Antimicrobial peptides are biosynthesis by organisms from all kingdoms as part of thedefense mechanism. Their mechanism of action is mainly related to a destabilization ofmembranes, and because of this, bacteria do not acquire resistance as easy as to traditionalantibiotics. Therefore, these molecules are currently under studied. Within this group ofpeptides, the mastopartane MP1, extracted from the venom of the Brazilian wasp PolybiaPaulista, is of great interest. This molecule has a potent antimicrobial action against adiversity of gram-positive and gram-negative bacteria, without producing hemolysis. Its osa short peptide, 14 amino acid long, with sequence I D W K K L L L D A A K Q I L-NH2and a low positive net charge (+2). This peptide exhibits a preferential interaction withanionic lipids, which could be attributed to electrostatic interactions, as has been describedfor other antimicrobial peptides. This may explain why these peptides are more activeagainst bacterial than mammalian membrane, the former being more negatively charged.However, the exact mechanism of action and differentiation of the target membrane is notknown. Therefore, our aim is to study the mechanism by which MP1 exerts its actionagainst Pseudomona aeruginosa, and what differentiates these cells from mammalian ones.In order to identify changes in the electrostatics due to the presence of the peptide, zetapotential measurements of the bacteria were performed in the presence of the peptide. Nochange in this parameter was observed when the peptide was added even at concentrationshigher than the minimum inhibitory concentration (MIC). In order to check the influence ofelectrostatics in the mechanism of action of the peptide, MIC was determined in thepresence and absence of salts, finding similar values. Both results indicate that thepreferential activity of this peptide against bacterial membranes would not be driven byelectrostatic interactions, which leads us to investigate effects related to the mechanicalproperties of the membrane. We are currently studying the effect of the peptide on lateraldiffusion in the bacterial membrane.