Unravelling the mechanism of action of "de novo" designed peptide P1 with model membranes and gram-positive and gram-negative bacteria.

Autor: Espeche JC; Laboratorio de Compuestos Bioactivos, Centro de Investigaciones en Biofísica Aplicada y Alimentos (CIBAAL), CONICET, Universidad Nacional de Santiago del Estero, RN 9, Km 1125, 4206, Santiago del Estero, Argentina., Martínez M; Laboratorio de Microbiología Molecular, Instituto de Microbiología Básica y Aplicada, Universidad Nacional de Quilmes, Roque Saenz Peña 352, B1876BXD, Bernal, Argentina., Maturana P; Laboratorio de Compuestos Bioactivos, Centro de Investigaciones en Biofísica Aplicada y Alimentos (CIBAAL), CONICET, Universidad Nacional de Santiago del Estero, RN 9, Km 1125, 4206, Santiago del Estero, Argentina., Cutró A; Laboratorio de Compuestos Bioactivos, Centro de Investigaciones en Biofísica Aplicada y Alimentos (CIBAAL), CONICET, Universidad Nacional de Santiago del Estero, RN 9, Km 1125, 4206, Santiago del Estero, Argentina; Facultad de Ciencias Medicas, Universidad Nacional de Santiago del Estero, Calle Reforma del 18 N ° 1234, 4200, Santiago del Estero, Argentina., Semorile L; Laboratorio de Microbiología Molecular, Instituto de Microbiología Básica y Aplicada, Universidad Nacional de Quilmes, Roque Saenz Peña 352, B1876BXD, Bernal, Argentina., Maffia PC; Laboratorio de Microbiología Molecular, Instituto de Microbiología Básica y Aplicada, Universidad Nacional de Quilmes, Roque Saenz Peña 352, B1876BXD, Bernal, Argentina., Hollmann A; Laboratorio de Compuestos Bioactivos, Centro de Investigaciones en Biofísica Aplicada y Alimentos (CIBAAL), CONICET, Universidad Nacional de Santiago del Estero, RN 9, Km 1125, 4206, Santiago del Estero, Argentina; Laboratorio de Microbiología Molecular, Instituto de Microbiología Básica y Aplicada, Universidad Nacional de Quilmes, Roque Saenz Peña 352, B1876BXD, Bernal, Argentina. Electronic address: ahollmann@conicet.gov.ar.
Jazyk: angličtina
Zdroj: Archives of biochemistry and biophysics [Arch Biochem Biophys] 2020 Oct 30; Vol. 693, pp. 108549. Date of Electronic Publication: 2020 Aug 21.
DOI: 10.1016/j.abb.2020.108549
Abstrakt: In the last years, the decreasing effectiveness of conventional antimicrobial-drugs has caused serious problems due to the rapid emergence of multidrug-resistant pathogens. This situation has brought attention to other antimicrobial agents like antimicrobial peptides (AMPs), for being considered an alternative to conventional drugs. These compounds target bacterial membranes for their activity, which gives them a broad spectrum of action and less probable resistance development. That is why the peptide-membrane interaction is a crucial aspect to consider in the study of AMPs. The aim of this work was the characterization of the "de novo" designed peptide P1, studying its interactions with model membranes (i.e. liposomes of DMPC:DMPG 5:1) in order to evaluate the final position of the peptide upon interacting with the membrane. Also, we tested the effects of the peptide in gram-positive and gram-negative bacteria. Later, by spectroscopic methods, the ability of the peptide to permeabilize the inner and outer membrane of E. coli and plasmatic membrane of S. aureus was assessed. The results obtained confirmed that P1 can disrupt both membranes, showing some difference in its activity as a function of the nature of each bacterial cell wall, confirming higher effects on gram-positive S. aureus. Finally, we also showed the ability of P1 to inhibit biofilms of that gram-positive bacterium. All data obtained in this work allowed us to propose a model, where the first interactions of the peptide with the bacterial envelope, seem to depend on the gram-negative and gram-positive cell wall structure. After that first interaction, the peptide is stabilized by Trp residues depth inserted into the hydrocarbon region, promoting several changes in the organization of the lipid bilayer, following a carpet-like mechanism, which results in permeabilization of the membrane, triggering the antimicrobial activity.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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