Ligand-lytic peptides for specific targeting of and parasites.

Introduction: Leishmaniasis and Chagas disease are major human neglected diseases, affecting an estimate of 12 and 6 to 8 million people worldwide, respectively. Current treatments for both diseases are highly toxic for the vertebrate host and lack specificity for the parasites, highlighting the need for the discovery of new therapies against these diseases. In this study, we tested the use of the lytic peptide and a construct that incorporates a ligand to bind the lytic peptide to protozoa membranes and screened them for protozoacidal activity.

Methods: We first screened parasite survival of luciferase expressing promastigotes and epimastigotes in the presence of or , and after 12, 48 and 96 h by measuring the parasite luciferase activity. In addition, High-Content Imaging Assay was used to evaluate the proliferation of intracellular amastigotes propagated inside murine macrophages after treatment with or .

Results: The lowest half maximal effective concentration observed after 48 h of incubation with and was lower against promastigotes than epimastigotes. treatment significantly reduced infection rate of macrophages amastigotes compared to the non-treated vehicle control; while treatment with was significant only at higher drug concentrations. Importantly, no significant cytotoxicity was observed when screened against intraperitoneal murine macrophages for either or treatments.

Discussion: Our results indicate that ligand-lytic peptide complexes are potential targets for therapeutic drugs that can selectively kill both extracellular and intracellular protozoa parasites stages with no significant toxicity to host cells.