title: Identification of Synthetic and Natural Host Defense Peptides with Leishmanicidal Activity.
abstract: Leishmaniaparasites are a major public health problem worldwide. Effective treatment of leishmaniasis is hampered by the high incidence of adverse effects to traditional drug therapy and the emergence of resistance to current therapeutics. A vaccine is currently not available. Host defense peptides have been investigated as novel therapeutic agents against a wide range of pathogens. Here we demonstrate that the antimicrobial peptide LL-37 and the three synthetic peptides E6, L-1018, and RI-1018 exhibit leishmanicidal activity against promastigotes and intramacrophage amastigotes ofLeishmania donovaniandLeishmania major We also report that theLeishmaniaprotease/virulence factor GP63 confers protection toLeishmaniafrom the cytolytic properties of alll-form peptides (E6, L-1018, and LL-37) but not thed-form peptide RI-1018. The results suggest that RI-1018, E6, and LL-37 are promising peptides to develop further into components for antileishmanial therapy.
authors.affiliation: Immunity and Infection Research Centre, Vancouver Coastal Health Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada Division of Experimental Biology, Sidra Medical and Research Center, Outpatient Clinic, Doha, Qatar.
authors.forename: A K
authors.initials: AK
authors.lastname: Marr
authors.affiliation: Immunity and Infection Research Centre, Vancouver Coastal Health Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Cen
authors.affiliation: Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada.
authors.forename: R E W
authors.initials: RE
authors.lastname: Hancock
authors.affiliation: Immunity and Infection Research Centre, Vancouver Coastal Health Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada robm@mail.ubc.ca.
authors.forename: W R
authors.initials: WR
authors.lastname: McMaster
mesh_terms: D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D054804:Cathelicidins / Q000494:pharmacology; D002460:Cell Line; D015870:Gene Expression; D006801:Humans; D007893:Leishmania donovani / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D018320:Leishmania major / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D008018:Life Cycle Stages / Q000187:drug effects* / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D030781:Organisms, Genetically Modified; D021261:Parasitic Sensitivity Tests; D065840:Protective Factors; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000494:pharmacology*; D013237:Stereoisomerism; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D000981:Antiprotozoal Agents; D054804:Cathelicidins; D054852:Small Molecule Libraries; D037521:Virulence Factors; D008666:Metalloendopeptidases; C055146:glycoprotein gp63, Leishmania