ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Parasite and Host
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1595333
This article is part of the Research TopicAdvancing Treatments for Protozoan Diseases: From Resistance Mechanisms to Novel TherapiesView all 12 articles
Ligand-lytic peptides for specific targeting of Leishmania major and Trypanosoma cruzi parasites
Provisionally accepted
- 1The University of Texas at El Paso, El Paso, Texas, United States
- 2Louisiana State University Agricultural Center, Baton Rouge, Louisiana, United States
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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 Hecate and a Ligand-Hecate construct that incorporates a ligand to bind the lytic peptide to protozoa membranes and screened them for protozoacidal activity. We first screened parasite survival of luciferase expressing Leishmania major promastigotes and Trypanosoma cruzi epimastigotes in the presence of Hecate or Ligand-Hecate, and after 12, 48 and 96 h by measuring the parasite luciferase activity. The lowest half maximal effective concentration observed after 48 h of incubation with Hecate and Ligand-Hecate was lower against L. major promastigotes than T. cruzi epimastigotes. High-Content Imaging Assay was used to evaluate the proliferation of intracellular L. major amastigotes propagated inside murine macrophages after treatment showed that Ligand-Hecate treatment significantly reduced infection rate of macrophages compared to the non-treated vehicle control; while treatment with Hecate was significant only at higher drug concentrations. Importantly, no significant cytotoxicity was observed when screened against intraperitoneal murine macrophages for either Hecate or Ligand-Hecate treatments. 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.
Keywords: Leishmaniasis, Chagas Disease, Lytic peptide, Hecate, Antimicrobial peptide, chemotherapy
Received: 17 Mar 2025; Accepted: 30 Apr 2025.
Copyright: © 2025 Iniguez, Rodriguez, Husseneder, Foil and Maldonado. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Lane Foil, Louisiana State University Agricultural Center, Baton Rouge, 16802, Louisiana, United States
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