In vitro and in vivo antimicrobial activity of two alpha-helical cathelicidin peptides and of their synthetic analogs.
Two alpha-helical antimicrobial peptides (BMAP-27 and -28) and four synthetic analogs were compared for in vitro and in vivo antimicrobial efficacy. All peptides proved active in vitro at micromolar concentrations against a range of clinical isolates, including antibiotic-resistant strains. BMAP-27 and two analogs were more effective towards Gram-negative, and BMAP-28 towards Gram-positive organisms. In addition, BMAP-28 provided some protection in vitro against human herpes simplex virus type 1 (HSV-1). The parent peptides and mBMAP-28 analog protected mice from lethal i.p. infections in an acute peritonitis model at peptide doses significantly lower than those toxic to the animals, suggesting a satisfactory therapeutic index.
Benincasa
Monica
M
Department of Biochemistry, Biophysics and Macromolecular Chemistry, University of Trieste, Via Giorgieri, 1, I-34127 Trieste, Italy. zanetti@icgeb.trieste.it
Skerlavaj
Barbara
B
Gennaro
Renato
R
Pellegrini
Antonio
A
Zanetti
Margherita
M
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D001419:Bacteria / Q000187:drug effects; D004195:Disease Models, Animal; D018259:Herpesvirus 1, Human / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D010538:Peritonitis / Q000188:drug therapy; D017433:Protein Structure, Secondary; D011506:Proteins / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D054804:Cathelicidins
D023181:Antimicrobial Cationic Peptides; C102359:BMAP-27; C102360:BMAP-28; D010446:Peptide Fragments; D011506:Proteins; D054804:Cathelicidins