{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:49:39Z","timestamp":1753890579753,"version":"3.41.2"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>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 <jats:italic>Hecate<\/jats:italic> and a <jats:italic>Ligand-Hecate<\/jats:italic> construct that incorporates a ligand to bind the lytic peptide to protozoa membranes and screened them for protozoacidal activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We first screened parasite survival of luciferase expressing <jats:italic>Leishmania major<\/jats:italic> promastigotes and <jats:italic>Trypanosoma cruzi<\/jats:italic> epimastigotes in the presence of <jats:italic>Hecate<\/jats:italic> or <jats:italic>Ligand-Hecate<\/jats:italic>, 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 <jats:italic>L. major<\/jats:italic> amastigotes propagated inside murine macrophages after treatment with <jats:italic>Hecate<\/jats:italic> or <jats:italic>Ligand-Hecate<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The lowest half maximal effective concentration observed after 48 h of incubation with <jats:italic>Hecate<\/jats:italic> and <jats:italic>Ligand-Hecate<\/jats:italic> was lower against <jats:italic>L. major<\/jats:italic> promastigotes than <jats:italic>T. cruzi<\/jats:italic> epimastigotes. <jats:italic>Ligand-Hecate<\/jats:italic> treatment significantly reduced infection rate of macrophages <jats:italic>L. major<\/jats:italic> amastigotes compared to the non-treated vehicle control; while treatment with <jats:italic>Hecate<\/jats:italic> was significant only at higher drug concentrations. Importantly, no significant cytotoxicity was observed when screened against intraperitoneal murine macrophages for either <jats:italic>Hecate<\/jats:italic> or <jats:italic>Ligand-Hecate<\/jats:italic> treatments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2025.1595333","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T05:45:30Z","timestamp":1748583930000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Ligand-lytic peptides for specific targeting of Leishmania major and Trypanosoma cruzi parasites"],"prefix":"10.3389","volume":"15","author":[{"given":"Eva","family":"Iniguez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felipe","family":"Rodriguez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Husseneder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lane","family":"Foil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa A.","family":"Maldonado","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035671","article-title":"Leishmaniasis worldwide and global estimates of its incidence","volume":"7","author":"Alvar","year":"2012","journal-title":"PLoS One"},{"first-page":"653","volume-title":"Global leishmaniasis surveillance updates 2023: 3 years of the NTD road map","year":"2024","key":"B2"},{"key":"B3","doi-asserted-by":"publisher","first-page":"974","DOI":"10.2307\/3284051","article-title":"Activity of lytic peptides against intracellular Trypanosoma cruzi amastigotes in vitro and parasitemias in mice","volume":"81","author":"Barr","year":"1995","journal-title":"J. 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