Molecular engineering of antimicrobial peptides inspired by ancestral marine biodiversity


PEPS X-life (2017-2018)
Project leader Agnès Delmas
β-defensins are cationic antimicrobial peptides widely distributed in vertebrates where they play a major role in the defense against infections. However, their activity is inhibited at high salinity, which could favor infections associated with certain human pathologies (cystic fibrosis). Big defensins composed of an b-defensin-like domain and a hydrophobic N-terminal domain (not present in vertebrate β-defensins) have only been described in ancestral marine species (limulids, molluscs, cephalochordates), which are poorly studied. These big defensins, which would be the ancestors of β-defensins, have a stable antimicrobial activity with very high salinity. We hypothesize that this hydrophobic domain has been maintained by evolution to preserve in these poor memory-immune species antimicrobial defenses effective at their physiological salinities. Based on a recently developed synthesis method and inspired by this ancestral marine biodiversity, a source of innovation, we will modify human β-defensins expressed by the pulmonary epithelium in order to make them active in saline medium such as tears or mucus of cystic fibrosis patients.
Partner 1 – UPR4301 CBM Orléans. Team « Aspects moléculaires du vivant » : Agnès Delmas, Vincent Aucagne, Karine Loth, Hervé Meudal
Partner 2 – Interactions Hôtes-Pathogènes-Environnements (UMR 5244 – Ifremer, CNRS, Université de Perpignan Via Domitia, Université de Montpellier) : Delphine Destoumieux-Garzόn, Agnès Vergnes
Partner 3 – Mucoviscidose et Bronchopathies Chroniques, Institut Pasteur, EA 2511 (Paris V) – Hôpital Cochin. Lhousseine Touqui.
Partner 4 – UGA, IAB Inserm U1209, CNRS UMR5309, Grenoble-Archamps, équipe : Immunologie Analytique des Pathologies Chroniques : Philippe Bulet, Sébatien Voisin