Functional characterization of temporin-she, a new broad-spectrum antibacterial and leishmanicidal temporin-SH paralog from the Sahara frog (Pelophylax saharicus) Andre, S. Raja, Z. Humblot, V. Piesse, C. Foulon, T. /Sereno, Denis /Oury, Bruno Ladram, A. frog antimicrobial peptide temporin-SHe broad-spectrum activity bacteria parasites secondary structure membrane disrupting mechanism scanning electron microscopy 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 alpha-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 differentLeishmaniaspecies 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. 2020 text https://www.documentation.ird.fr/hor/PAR00021702 PAR00021702 Andre S., Raja Z., Humblot V., Piesse C., Foulon T., Sereno Denis, Oury Bruno, Ladram A.. Functional characterization of temporin-she, a new broad-spectrum antibacterial and leishmanicidal temporin-SH paralog from the Sahara frog (Pelophylax saharicus). 2020, 21 (18), 6713 [19 p.] EN