Quaternized 1,2,3-Triazolyl Content and Modulation Potentiate Antibacterial and Antifungal Activities of Amphipathic Peptoids
Year: 2024
Type: article
Abstract: Bioinspired from cationic antimicrobial peptides, sequence-defined triazolium-grafted peptoid oligomers (6- to 12-mer) were designed to adopt an amphipathic helical polyproline I-type structure. Their evaluation on a panel of bacterial strains ( Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis ), pathogenic fungi ( Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus ), and human cells (hRBC, BEAS-2B, Caco-2, HaCaT, and HepG2) enabled the identification of two heptamers with improved activity to selectively fight Staphylococcus aureus pathogens. Modulation of parameters such as the nature of the triazolium and hydrophobic/lipophilic side chains, the charge content, and the sequence length drastically potentiates activity and selectivity. Besides, the ability to block the proinflammatory effect induced by lipopolysaccharide or lipoteichoic acid was also explored. Finally, biophysical studies by circular dichroism and fluorescence spectroscopies strongly supported that the bactericidal effect of these triazolium-grafted oligomers was primarily due to the selective disruption of the bacterial membrane.
Source: ACS Infectious Diseases
Institutions: Centre National de la Recherche Scientifique, Université Clermont Auvergne, Institut de Chimie de Clermont-Ferrand, Clermont Auvergne INP, Laboratoire Microorganismes Génome et Environnement, Institut de Chimie de Strasbourg, Université de Strasbourg, Aix-Marseille Université, Centrale Méditerranée, Institut des Sciences Moléculaires de Marseille, Institut de Chimie Radicalaire, Lyon 1 Université, École Normale Supérieure de Lyon, Inserm, Centre International de Recherche en Infectiologie
Language: English
Subfield: Microbiology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: G177041573, G1816956845, G2098545568, Par-delà les frontières, l'Université de Strasbourg, G254877862, G2744136243, Engineering antibacterial cationic amphipathic peptidomimetics for targeting biofilm-embedded and intracellular bacteria, G471331628, New Antibiotics Tackling mUlti-Resistance by acting on Alternative bacteriaL tARgets in Synergy with mEmbrane-disruptiNg AntimicrobiaL peptides., CAP 20-25, G637341188, Synergistic action of a photosensitizer and antimicrobial peptides for superbugs destruction, G7240651115
OpenAlex ID: W4403329283