Activity of an engineered synthetic killer peptide on Leishmania major and Leishmania infantum promastigotes.
This study was undertaken to analyze the effect of an engineered, killer decapeptide (KP) on Leishmania major and Leishmania infantum promastigotes. The KP was synthesized on the basis of the sequence of a recombinant, single-chain anti-idiotypic antibody acting as a functional internal image of a yeast killer toxin. The evaluation of in vitro inhibitory activity of KP on L. major and L. infantum, release of intracellular green fluorescent protein (GFP) molecules by L. major, DNA fragmentation, and ultrastructural analysis (TEM) of L. infantum upon KP treatment were performed. KP presented antiproliferative and leishmanicidal activity with LC(50)/1 day of 58 and 72 microM for L. major and L. infantum, respectively. A dose-dependent decrease in proliferation and increase of killing of promastigotes was seen after KP treatment. No DNA fragmentation in L. infantum promastigotes or release of intracellular GFP molecules on peptide treatment of a GFP expressing L. major clone was demonstrated. Moreover the plasma-membrane was not disrupted, but, by TEM analysis, intracellular damage was observed.
Department of Clinical and Biological Sciences, University of Torino, at S. Luigi Gonzaga Hospital, Regione Gonzole 10, 10143 Orbassano (To), Italy. dianella.savoia@unito.it
Dianella
D
Savoia
Sara
S
Scutera
Stefania
S
Raimondo
Stefania
S
Conti
Walter
W
Magliani
Luciano
L
Polonelli
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D044602:Cellulases / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D015198:Designer Drugs / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D049452:Green Fluorescent Proteins; D007202:Indicators and Reagents; D018314:Leishmania infantum / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D018320:Leishmania major / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D008751:Methylene Blue; D046529:Microscopy, Electron, Transmission; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects
D000911:Antibodies, Monoclonal; D000981:Antiprotozoal Agents; D015198:Designer Drugs; D007202:Indicators and Reagents; D010455:Peptides; D049452:Green Fluorescent Proteins; D044602:Cellulases; D008751:Methylene Blue