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Here, we show the antileishmanial activity of DODAB nano-sized cationic bilayer fragments on stationary-phase promastigotes and amastigotes of Leishmania amazonensis, the causative agent of cutaneous leishmaniasis. Upon treatment with DODAB, we analyzed the parasite surface zeta-potential, parasite viability, cellular structural modifications, and intracellular proliferation. The DODAB cytotoxic effect was dose-dependent, with a median effective concentration (EC50) of 25 \u00b5M for both life-cycle stages, comparable to the reported data for bacteria and fungi. The treatment with DODAB changed the membrane zeta-potential from negative to positive, compromised the parasite\u2019s morphology, affected the cell size regulation, caused a loss of intracellular organelles, and probably dysregulated the plasma membrane permeability without membrane disruption. Moreover, the parasites that survived after treatment induced small parasitophorous vacuoles and failed to proliferate inside macrophages. In conclusion, DODAB displayed antileishmanial activity, and it remains to be elucidated how DODAB acts on the protozoan membrane. Understanding this mechanism can provide insights into the development of new parasite-control strategies.<\/jats:p>","DOI":"10.3390\/molecules25235741","type":"journal-article","created":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T22:15:36Z","timestamp":1607638536000},"page":"5741","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Effect of DODAB Nano-Sized Cationic Bilayer Fragments against Leishmania amazonensis"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8282-5708","authenticated-orcid":false,"given":"Thalita C. S.","family":"Ferreira","sequence":"first","affiliation":[{"name":"Departamento de Parasitologia, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade de S\u00e3o Paulo, S\u00e3o Paulo, SP 05508-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ismael P.","family":"Sauter","sequence":"additional","affiliation":[{"name":"Departamento de Parasitologia, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade de S\u00e3o Paulo, S\u00e3o Paulo, SP 05508-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lina","family":"Borda-Samper","sequence":"additional","affiliation":[{"name":"Departamento de Parasitologia, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade de S\u00e3o Paulo, S\u00e3o Paulo, SP 05508-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8250-9788","authenticated-orcid":false,"given":"Enyd","family":"Bentivoglio","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade de S\u00e3o Paulo, S\u00e3o Paulo, SP 05508-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6117-7630","authenticated-orcid":false,"given":"Jarina P.","family":"DaMata","sequence":"additional","affiliation":[{"name":"Departamento de Parasitologia, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade de S\u00e3o Paulo, S\u00e3o Paulo, SP 05508-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noemi N.","family":"Taniwaki","sequence":"additional","affiliation":[{"name":"Instituto Adolfo Lutz, S\u00e3o Paulo, SP 02146-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patr\u00edcio R.","family":"Orrego","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias de la Salud, Departamento Biom\u00e9dico, Universidad de Antofagasta, Antofagasta, CP 1270300, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge E.","family":"Araya","sequence":"additional","affiliation":[{"name":"Facultad de Ci\u00eancias de la Salud, Departamento de Tecnolog\u00eda M\u00e9dica, Universidad de Antofagasta, Antofagasta, CP 1270300, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0161-5800","authenticated-orcid":false,"given":"Nilton","family":"Lincopan","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade de S\u00e3o Paulo, S\u00e3o Paulo, SP 05508-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6536-4647","authenticated-orcid":false,"given":"Mauro","family":"Cortez","sequence":"additional","affiliation":[{"name":"Departamento de Parasitologia, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade de S\u00e3o Paulo, S\u00e3o Paulo, SP 05508-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Akhoundi, M., Kuhls, K., Cannet, A., Vot\u00fdpka, J., Marty, P., Delaunay, P., and Sereno, D. 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