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.
Copyright © 2016, American Society for Microbiology. All Rights Reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Antimicrobial Cationic Peptides
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Antiprotozoal Agents / chemical synthesis
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Antiprotozoal Agents / pharmacology*
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Cathelicidins / pharmacology
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Cell Line
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Gene Expression
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Humans
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Leishmania donovani / drug effects*
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Leishmania donovani / genetics
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Leishmania donovani / growth & development
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Leishmania major / drug effects*
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Leishmania major / genetics
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Leishmania major / growth & development
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Life Cycle Stages / drug effects*
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Life Cycle Stages / genetics
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Macrophages / drug effects
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Macrophages / parasitology
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Metalloendopeptidases / genetics
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Metalloendopeptidases / metabolism
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Organisms, Genetically Modified
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Parasitic Sensitivity Tests
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Protective Factors
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Small Molecule Libraries / chemical synthesis
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Small Molecule Libraries / pharmacology*
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Stereoisomerism
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Virulence Factors / genetics
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Virulence Factors / metabolism
Substances
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Antimicrobial Cationic Peptides
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Antiprotozoal Agents
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Cathelicidins
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Small Molecule Libraries
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Virulence Factors
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Metalloendopeptidases
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glycoprotein gp63, Leishmania