Identification of synthetic and natural host defense peptides with leishmanicidal activity

Leishmania parasites 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 of Leishmania donovani and Leishmania major. We also report that the Leishmania protease/virulence factor GP63 confers protection to Leishmania from the cytolytic properties of all L-form peptides (E6, L-1018, and LL-37) but not the D-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.