Studies of the interaction of the antimicrobial peptide Polymyxin with bacterial membrane models

FEITO FRANCISCO ANDRÉS; MADRID ROSSANA; DUPUY FERNANDO

Rosario

Congreso; L Reunión Anual de la Sociedad Argentina de Biofísica; 2022

Due to the increase of new mechanisms of resistance of sensitive cells to traditional antibiotics, it is necessary to develop novel strategies for the control of microbial growth. In this sense, antimicrobial peptides represent a valuable alternative, due to their broad spectrum of action. Therefore, the study of the mechanism of action of antimicrobial peptides in the interaction with biological membranes is of special interest, since this interaction can affect properties of the lipid bilayer such as selective permeability and the curvature of the interface. Certain cationic peptides, such as Polymyxin E or also known as Colistin, cause cell death by inserting into the lipid membrane of Gram-negative bacteria by a yet unknown mechanism, acting as antimicrobial agents. To gain knowledge about this interaction and the mechanism of action of this peptide at molecular level, we worked with two different models of bacterial membranes. On the one hand, we worked with mimetic membrane models using Langmuir-Blodgett phospholipid monolayers. Langmuir isotherms and fixed – area Gibbs isotherms were performed to study the effect of pH and lipid composition on Polymyxin interaction, measuring surface pressure and surface potential simultaneously. On the other hand, lipid bilayer models were studied, using medium-sized unilamellar liposomes or LUVs, in the presence and absence of the peptide by means of fluorescence spectroscopy with polarized light. The results of this work indicate that the interaction of Polymyxin with lipid monolayers is modulated by the charge state of the membrane. It was also demonstrated that the interaction with this peptide influences the degree of order and fluidity of the lipid bilayers, showing two differentiated order states in both phases of the lipidic film.