Antimicrobial Bombinin-like Peptide 3 Selectively Recognizes and Inserts into Bacterial Biomimetic Bilayers in Multiple Steps.

Autor: Annaval T; Unité de Génie Enzymatique et Cellulaire UMR 7025 CNRS, Université de Picardie Jules Verne, Amiens 80039, France.; Institut de Biologie Structurale, UMR 5075, Université Grenoble Alpes, CNRS, CEA, Grenoble 38000, France., Ramos-Martín F; Unité de Génie Enzymatique et Cellulaire UMR 7025 CNRS, Université de Picardie Jules Verne, Amiens 80039, France., Herrera-León C; Unité de Génie Enzymatique et Cellulaire UMR 7025 CNRS, Université de Picardie Jules Verne, Amiens 80039, France., Adélaïde M; Unité de Génie Enzymatique et Cellulaire UMR 7025 CNRS, Université de Picardie Jules Verne, Amiens 80039, France., Antonietti V; Agents Infectieux, Résistance et Chimiothérapie, AGIR UR 4294, Université de Picardie Jules Verne, UFR de Pharmacie, Amiens 80037, France., Buchoux S; Unité de Génie Enzymatique et Cellulaire UMR 7025 CNRS, Université de Picardie Jules Verne, Amiens 80039, France., Sonnet P; Agents Infectieux, Résistance et Chimiothérapie, AGIR UR 4294, Université de Picardie Jules Verne, UFR de Pharmacie, Amiens 80037, France., Sarazin C; Unité de Génie Enzymatique et Cellulaire UMR 7025 CNRS, Université de Picardie Jules Verne, Amiens 80039, France., D'Amelio N; Unité de Génie Enzymatique et Cellulaire UMR 7025 CNRS, Université de Picardie Jules Verne, Amiens 80039, France.
Jazyk: angličtina
Zdroj: Journal of medicinal chemistry [J Med Chem] 2021 Apr 22; Vol. 64 (8), pp. 5185-5197. Date of Electronic Publication: 2021 Apr 14.
DOI: 10.1021/acs.jmedchem.1c00310
Abstrakt: Bombinins are a wide family of antimicrobial peptides from Xenopus skin. By sequence clustering, we highlighted at least three families named A, B, and H, which might exert antibacterial activity by different modes of action. In this work, we study bombinin-like peptide 3 (BLP-3) as a nonhemolytic representative of the quite unexplored class A due to its appealing activity toward WHO-priority-list bacteria such as Neisseria , Pseudomonas aeruginosa , and Staphylococcus aureus . A marked preference for cardiolipin and phosphatidylglycerol head groups, typically found in bacteria, is proven with biomimetic membranes studied by liquid and solid NMR and MD simulations. BLP-3 gets structured upon interaction and penetrates deeply into the bilayer in two steps involving a superficial insertion of key side chains and subsequent internalization. All along the pathway, a fundamental role is played by lysine residues in the conserved region 11-19, which act in synergy with other key residues.
Databáze: MEDLINE