Open AccessPeptidoglycan potentiates the membrane disrupting effect of the carboxyamidated form of DMS-DA6, a Gram-positive selective antimicrobial peptide isolated from Pachymedusa dacnicolor skin
Author(s) -
Sébastien Cardon,
Emmanuelle Sachon,
Ludovic Carlier,
Thierry Drujon,
Astrid Walrant,
Estefanía Alemán-Navarro,
Verónica Martínez-Osorio,
Dominique Guianvarc’h,
Sandrine Sagan,
Yannick Fleury,
Rodrigue Marquant,
Christophe Piesse,
Yvonne Rosenstein,
Constance Auvynet,
C. Lacombe
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0205727
Subject(s) - peptidoglycan , gram positive bacteria , enterococcus faecium , bacteria , antimicrobial peptides , microbiology and biotechnology , antimicrobial , peptide , staphylococcus aureus , gram negative bacteria , antibiotics , biology , lipid ii , biochemistry , chemistry , escherichia coli , gene , genetics
The occurrence of nosocomial infections has been on the rise for the past twenty years. Notably, infections caused by the Gram-positive bacteria Staphylococcus aureus represent a major clinical problem, as an increase in antibiotic multi-resistant strains has accompanied this rise. There is thus a crucial need to find and characterize new antibiotics against Gram-positive bacteria, and against antibiotic-resistant strains in general. We identified a new dermaseptin, DMS-DA6, produced by the skin of the Mexican frog Pachymedusa dacnicolor , with specific antibacterial activity against Gram-positive bacteria. This peptide is particularly effective against two multiple drug-resistant strains Enterococcus faecium BM4147 and Staphylococcus aureus DAR5829, and has no hemolytic activity. DMS-DA6 is naturally produced with the C-terminal carboxyl group in either the free or amide forms. By using Gram-positive model membranes and different experimental approaches, we showed that both forms of the peptide adopt an α-helical fold and have the same ability to insert into, and to disorganize a membrane composed of anionic lipids. However, the bactericidal capacity of DMS-DA6-NH 2 was consistently more potent than that of DMS-DA6-OH. Remarkably, rather than resulting from the interaction with the negatively charged lipids of the membrane, or from a more stable conformation towards proteolysis, the increased capacity to permeabilize the membrane of Gram-positive bacteria of the carboxyamidated form of DMS-DA6 was found to result from its enhanced ability to interact with peptidoglycan.