title: Antibacterial and leishmanicidal activities of temporin-SHd, a 17-residue long membrane-damaging peptide.
abstract: Temporins are a family of short antimicrobial peptides (8-17 residues) that mostly show potent activity against Gram-positive bacteria. Herein, we demonstrate that temporin-SHd, a 17-residue peptide with a net charge of +2 (FLPAALAGIGGILGKLF(amide)), expressed a broad spectrum of antimicrobial activity. This peptide displayed potent antibacterial activities against Gram-negative and Gram-positive bacteria, including multi-drug resistant Staphylococcus aureus strains, as well as antiparasitic activity against promastigote and the intracellular stage (amastigote) of Leishmania infantum, at concentration not toxic for the macrophages. Temporin-SHd that is structured in a non-amphipathic α-helix in anionic membrane-mimetic environments, strongly and selectively perturbs anionic bilayer membranes by interacting with the polar head groups and acyl region of the phospholipids, with formation of regions of two coexisting phases: one phase rich in peptide and the other lipid-rich. The disruption of lipid packing within the bilayer may lead to the formation of transient pores and membrane permeation/disruption once a threshold peptide accumulation is reached. To our knowledge, Temporin-SHd represents the first known 17-residue long temporin expressing such broad spectrum of antimicrobial activity including members of the trypanosomatidae family. Additionally, since only a few shorter members (13 residues) of the temporin family are known to display antileishmanial activity (temporins-TA, -TB and -SHa), SHd is an interesting tool to analyze the antiparasitic mechanism of action of temporins.
authors.affiliation: UPMC Univ Paris 06, ER3 Biogenèse des Signaux Peptidiques, F-75005 Paris, France.
authors.forename: Feten
authors.initials: F
authors.lastname: Abbassi
authors.forename: Zahid
authors.initials: Z
authors.lastname: Raja
authors.forename: Bruno
authors.initials: B
authors.lastname: Oury
authors.forename: Elodie
authors.initials: E
authors.lastname: Gazanion
authors.forename: Christophe
authors.initials: C
authors.lastname: Piesse
authors.forename: Denis
authors.initials: D
authors.lastname: Sereno
authors.forename: Pierre
authors.initials: P
authors.lastname: Nicolas
authors.forename: Thierry
authors.initials: T
authors.lastname: Foulon
authors.forename: Ali
authors.initials: A
authors.lastname: Ladram
mesh_terms: D000595:Amino Acid Sequence; D029845:Amphibian Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000890:Anti-Infective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D002942:Circular Dichroism; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D020128:Inhibitory Concentration 50; D018314:Leishmania infantum / Q000187:drug effects* / Q000254:growth & development; D008051:Lipid Bilayers / Q000737:chemistry; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D008969:Molecular Sequence Data; D010743:Phospholipids / Q000737:chemistry; D011506:Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D011898:Ranidae / Q000378:metabolism*; D012867:Skin / Q000378:metabolism; D060327:Solid-Phase Synthesis Techniques; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014345:Trypanosoma / Q000187:drug effects* / Q000254:growth & development
chemical_list: D029845:Amphibian Proteins; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D010743:Phospholipids; D011506:Proteins; C104501:temporin