Effect of DODAB Nano-Sized Cationic Bilayer Fragments against Leishmania amazonensis

Autor(es)

Ferreira, Thalita C. S. ^[1] ; Sauter, Ismael P. ^[1] ; Borda-Samper, Lina ^[1] ; Bentivoglio, Enyd ^[2] ; DaMata, Jarina P. ^[1] ; Taniwaki, Noemi N. ^[3] ; Orrego, Patricio R. ^[4] ; Araya, Jorge E. ^[5] ; Lincopan, Nilton ^[2] ; Cortez, Mauro ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Parasitol, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, BR-05508000 Sao Paulo, SP - Brazil

^[3] Adolfo Lutz Inst, BR-02146000 Sao Paulo, SP - Brazil

^[4] Univ Antofagasta, Fac Ciencias Salud, Dept Biomed, Antofagasta 1270300 - Chile

^[5] Univ Antofagasta, Fac Ciencias Salud, Dept Tecnol Med, Antofagasta 1270300 - Chile

• Tipo de documento: Artigo Científico
• Fonte: Molecules; v. 25, n. 23 DEC 2020.
• Citações Web of Science: 1

Resumo

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 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 mu M 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. (AU)

• Processo FAPESP: 13/14087-0 - Estudo do papel dos receptores do tipo toll (TLRs) na indução de CD200 em macrófagos murinos infectados com Leishmania (L.) amazonensis
• Beneficiário: Ismael Pretto Sauter
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/15254-8 - Envolvimento de CD200 na infectividade de isolados de L. (L.) amazonensis associados à Leishmaniose cutânea (LCL) e Leishmaniose cutânea difusa (LCD)
• Beneficiário: Lina Borda Samper
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 16/08593-9 - Pan-resistoma de Klebsiella pneumoniae e Escherichia coli produtoras de beta-lactamases (KPC-2, CTX-M-8, CTX-M-15) endêmicas no Brasil
• Beneficiário: Nilton Erbet Lincopan Huenuman
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/24105-3 - Imunobiologia de Leishmania spp.: estudo do papel de CD200 e biogênese do vacúolo parasitóforo em células fagocíticas infectadas por Leishmania
• Beneficiário: Mauro Javier Cortez Véliz
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores