| Autor: |
André S; Sorbonne Université, CNRS, Institut de Biologie Paris-Seine, IBPS, BIOSIPE, F-75252 Paris, France.; Cell death in host-pathogen interactions,CNRS-ERL3649, Université de Paris, 75006 Paris, France., Raja Z; Sorbonne Université, CNRS, Institut de Biologie Paris-Seine, IBPS, BIOSIPE, F-75252 Paris, France., Humblot V; FEMTO-ST Institute, UMR CNRS 6174, Université Bourgogne Franche-Comté, 25030 Besançon CEDEX, France., Piesse C; Sorbonne Université, CNRS, Institut de Biologie Paris-Seine, IBPS, Peptide Synthesis Facility, F-75252 Paris, France., Foulon T; Sorbonne Université, CNRS, Institut de Biologie Paris-Seine, IBPS, BIOSIPE, F-75252 Paris, France., Sereno D; IRD, Université de Montpellier, MiVegec, 34394 Montpellier CEDEX 5, France.; IRD, Université de Montpellier, InterTryp, 34394 Montpellier CEDEX 5, France., Oury B; IRD, Université de Montpellier, InterTryp, 34394 Montpellier CEDEX 5, France., Ladram A; Sorbonne Université, CNRS, Institut de Biologie Paris-Seine, IBPS, BIOSIPE, F-75252 Paris, France. |
| Abstrakt: |
Amphibian skin is a promising natural resource for antimicrobial peptides (AMPs), key effectors of innate immunity with attractive therapeutic potential to fight antibiotic-resistant pathogens. Our previous studies showed that the skin of the Sahara Frog ( Pelophylax saharicus ) contains broad-spectrum AMPs of the temporin family, named temporins-SH. Here, we focused our study on temporin-SHe, a temporin-SHd paralog that we have previously identified in this frog but was never structurally and functionally characterized. We synthesized and determined the structure of temporin-SHe. This non-amphipathic α-helical peptide was demonstrated to strongly destabilize the lipid chain packing of anionic multilamellar vesicles mimicking bacterial membranes. Investigation of the antimicrobial activity revealed that temporin-SHe targets Gram-negative and Gram-positive bacteria, including clinical isolates of multi-resistant Staphylococcus aureus strains. Temporin-SHe exhibited also antiparasitic activity toward different Leishmania species responsible for visceral leishmaniasis, as well as cutaneous and mucocutaneous forms. Functional assays revealed that temporin-SHe exerts bactericidal effects with membrane depolarization and permeabilization, via a membranolytic mechanism observed by scanning electron microscopy. Temporin-SHe represents a new member of the very limited group of antiparasitic temporins/AMPs. Despite its cytotoxicity, it is nevertheless an interesting tool to study the AMP antiparasitic mechanism and design new antibacterial/antiparasitic agents. |
