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Plasmodium sporozoites are potentially exposed to these cytotoxic molecules in the hemolymph and salivary glands of mosquitoes, as well as in the skin, blood, and liver of the mammalian host. Here, we show that sporozoites are resistant to bacteriolytic concentration of cecropin B, a cationic amphipathic antimicrobial insect peptide. Intriguingly, anti-tumoral cell-penetrating peptides derived from the anti-apoptotic protein AAC11 killed P. berghei and P. falciparum sporozoites. Using dynamic imaging, we demonstrated that the most cytotoxic peptide, called RT39, did not significantly inhibit the sporozoite motility until the occurrence of a fast permeabilization of the parasite membrane by the peptide. Concomitantly, the cytosolic fluorescent protein constitutively expressed by sporozoites leaked from the treated parasite body while To-Pro 3 and FITC-labeled RT39 internalized, respectively, binding to the nucleic acids and membranes of sporozoites. This led to an increase in the parasite granularity as assessed by flow cytometry. Most permeabilization events started at the parasite\u2019s posterior end, resulting in the appearance of a fluorescent dot in the anterior part of sporozoites. Understanding and exploiting the susceptibility of sporozoites and other plasmodial stages to membranolytic molecules might foster strategies to eliminate the parasite and block its transmission.<\/jats:p>","DOI":"10.3390\/microorganisms12030480","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T05:20:32Z","timestamp":1709011232000},"page":"480","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Killing of Plasmodium Sporozoites by Basic Amphipathic \u03b1-Helical Fusion Peptides"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0019-5122","authenticated-orcid":false,"given":"Manuela C.","family":"Aguirre-Botero","sequence":"first","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, Malaria Infection and Immunity, BioSPC, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Aliprandini","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, Malaria Infection and Immunity, BioSPC, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anisha","family":"Gladston","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, Malaria Infection and Immunity, BioSPC, 75015 Paris, France"},{"name":"Department of Life Sciences, Imperial College London, London SW7 2AZ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4476-856X","authenticated-orcid":false,"given":"Olga","family":"Pacios","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, Malaria Infection and Immunity, BioSPC, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Miyazawa Martins","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, Malaria Infection and Immunity, BioSPC, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3747-255X","authenticated-orcid":false,"given":"Jean-Luc","family":"Poyet","sequence":"additional","affiliation":[{"name":"INSERM UMRS976, Institut de Recherche Saint-Louis, H\u00f4pital Saint-Louis, 75010 Paris, France"},{"name":"Universit\u00e9 Paris Cit\u00e9, 75012 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rogerio","family":"Amino","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, Malaria Infection and Immunity, BioSPC, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.gde.2006.06.012","article-title":"The developmental migration of Plasmodium in mosquitoes","volume":"16","author":"Vlachou","year":"2006","journal-title":"Curr. 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