Effect of DODAB Nano-Sized Cationic Bilayer Fragments against <i>Leishmania amazonensis</i>

The dioctadecyldimethylammonium bromide (DODAB) is a double-chained cationic lipid with potent bactericide and fungistatic activities; however, its toxicity on protozoan parasites is still unknown. Here, we show the antileishmanial activity of DODAB nano-sized cationic bilayer fragments on stationar...

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Main Authors: Thalita C. S. Ferreira, Ismael P. Sauter, Lina Borda-Samper, Enyd Bentivoglio, Jarina P. DaMata, Noemi N. Taniwaki, Patrício R. Orrego, Jorge E. Araya, Nilton Lincopan, Mauro Cortez
Format: Article
Language:English
Published: MDPI AG 2020-12-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/25/23/5741
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author Thalita C. S. Ferreira
Ismael P. Sauter
Lina Borda-Samper
Enyd Bentivoglio
Jarina P. DaMata
Noemi N. Taniwaki
Patrício R. Orrego
Jorge E. Araya
Nilton Lincopan
Mauro Cortez
author_facet Thalita C. S. Ferreira
Ismael P. Sauter
Lina Borda-Samper
Enyd Bentivoglio
Jarina P. DaMata
Noemi N. Taniwaki
Patrício R. Orrego
Jorge E. Araya
Nilton Lincopan
Mauro Cortez
author_sort Thalita C. S. Ferreira
collection DOAJ
description The dioctadecyldimethylammonium bromide (DODAB) is a double-chained cationic lipid with potent bactericide and fungistatic activities; however, its toxicity on protozoan parasites is still unknown. Here, we show the antileishmanial activity of DODAB nano-sized cationic bilayer fragments on stationary-phase promastigotes and amastigotes of <i>Leishmania amazonensis</i>, 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 (EC<sub>50</sub>) of 25 µM 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’s 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.
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spelling doaj.art-97064c9eeecb48a4aa19d12ef1807f072023-11-20T23:35:49ZengMDPI AGMolecules1420-30492020-12-012523574110.3390/molecules25235741Effect of DODAB Nano-Sized Cationic Bilayer Fragments against <i>Leishmania amazonensis</i>Thalita C. S. Ferreira0Ismael P. Sauter1Lina Borda-Samper2Enyd Bentivoglio3Jarina P. DaMata4Noemi N. Taniwaki5Patrício R. Orrego6Jorge E. Araya7Nilton Lincopan8Mauro Cortez9Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP 05508-000, BrazilDepartamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP 05508-000, BrazilDepartamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP 05508-000, BrazilDepartamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP 05508-000, BrazilDepartamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP 05508-000, BrazilInstituto Adolfo Lutz, São Paulo, SP 02146-000, BrazilFacultad de Ciencias de la Salud, Departamento Biomédico, Universidad de Antofagasta, Antofagasta, CP 1270300, ChileFacultad de Ciências de la Salud, Departamento de Tecnología Médica, Universidad de Antofagasta, Antofagasta, CP 1270300, ChileDepartamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP 05508-000, BrazilDepartamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP 05508-000, BrazilThe dioctadecyldimethylammonium bromide (DODAB) is a double-chained cationic lipid with potent bactericide and fungistatic activities; however, its toxicity on protozoan parasites is still unknown. Here, we show the antileishmanial activity of DODAB nano-sized cationic bilayer fragments on stationary-phase promastigotes and amastigotes of <i>Leishmania amazonensis</i>, 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 (EC<sub>50</sub>) of 25 µM 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’s 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.https://www.mdpi.com/1420-3049/25/23/5741antileishmanial activitycationic bilayer fragmentsdioctadecyldimethylammonium bromide (DODAB)<i>Leishmania amazonensis</i>
spellingShingle Thalita C. S. Ferreira
Ismael P. Sauter
Lina Borda-Samper
Enyd Bentivoglio
Jarina P. DaMata
Noemi N. Taniwaki
Patrício R. Orrego
Jorge E. Araya
Nilton Lincopan
Mauro Cortez
Effect of DODAB Nano-Sized Cationic Bilayer Fragments against <i>Leishmania amazonensis</i>
Molecules
antileishmanial activity
cationic bilayer fragments
dioctadecyldimethylammonium bromide (DODAB)
<i>Leishmania amazonensis</i>
title Effect of DODAB Nano-Sized Cationic Bilayer Fragments against <i>Leishmania amazonensis</i>
title_full Effect of DODAB Nano-Sized Cationic Bilayer Fragments against <i>Leishmania amazonensis</i>
title_fullStr Effect of DODAB Nano-Sized Cationic Bilayer Fragments against <i>Leishmania amazonensis</i>
title_full_unstemmed Effect of DODAB Nano-Sized Cationic Bilayer Fragments against <i>Leishmania amazonensis</i>
title_short Effect of DODAB Nano-Sized Cationic Bilayer Fragments against <i>Leishmania amazonensis</i>
title_sort effect of dodab nano sized cationic bilayer fragments against i leishmania amazonensis i
topic antileishmanial activity
cationic bilayer fragments
dioctadecyldimethylammonium bromide (DODAB)
<i>Leishmania amazonensis</i>
url https://www.mdpi.com/1420-3049/25/23/5741
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