Quaternized 1,2,3-Triazolyl Content and Modulation Potentiate Antibacterial and Antifungal Activities of Amphipathic Peptoids
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 (<i>Escherichia coli</i>, <i>Pseudomonas aeruginosa</i>, <i>Staphylococcus aureus</i>, and <i>Enterococcus faecalis</i>), pathogenic fungi (<i>Candida albicans</i>, <i>Cryptococcus neoformans</i>, and <i>Aspergillus fumigatus</i>), and human cells (hRBC, BEAS-2B, Caco-2, HaCaT, and HepG2) enabled the identification of two heptamers with improved activity to selectively fight <i>Staphylococcus aureus</i> 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.
Authors
- Kathakali De (ORCID: https://orcid.org/0009-0000-6875-6611)
- Burkhard Bechinger (ORCID: https://orcid.org/0000-0001-5719-6073)
- Christiane Forestier (ORCID: https://orcid.org/0000-0002-0005-9673)
- Olivier Roy (ORCID: https://orcid.org/0000-0002-7238-8708)
- C. Guerinot
- Sophie Faure (ORCID: https://orcid.org/0000-0001-5033-9481)
- Elise Courvoisier‐Dezord (ORCID: https://orcid.org/0000-0002-4256-3528)
- Jérôme Josse (ORCID: https://orcid.org/0000-0001-6780-9646)
- Christopher Aisenbrey (ORCID: https://orcid.org/0000-0001-9426-4215)
- Marc Maresca (ORCID: https://orcid.org/0000-0002-3585-4765)
- Frédéric Laurent (ORCID: https://orcid.org/0000-0003-0609-9091)
- M. Malige
- Nicolas Charbonnel
- Nicolas Vidal (ORCID: https://orcid.org/0000-0001-5032-3199)
Institutions
- Université Claude Bernard Lyon 1 (FR)
- École Normale Supérieure de Lyon (FR)
- Centre National de la Recherche Scientifique (FR)
- Université Clermont Auvergne (FR)
- Aix-Marseille Université (FR)
- Institut de Chimie Radicalaire (FR)
- Institut de Chimie de Strasbourg (FR)
- Laboratoire Microorganismes Génome et Environnement (FR)
- Institut de Chimie de Clermont-Ferrand (FR)
- Centre International de Recherche en Infectiologie (FR)
Publication Details
- Journal
- ACS Infectious Diseases
- Published
- 2024-10-11
- DOI
- https://doi.org/10.1021/acsinfecdis.4c00591
- Citations
- 2
- Primary Topic
- Antimicrobial Peptides and Activities
- Type
- article
- Field-Weighted Citation Impact
- 0.69
Funders
- Agence Nationale de la Recherche
- Indo-French Centre for the Promotion of Advanced Research
- Région Auvergne-Rhône-Alpes
- Conseil régional du Grand Est
- Université Clermont-Auvergne