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

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: Molecules; v. 25, n. 23 DEC 2020.
• Web of Science Citations: 1

Abstract

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)

• FAPESP's process: 13/14087-0 - Study of the role of Toll-like receptors (TLRs) on CD200 induction in murine macrophages infected with Leishmania (L.) amazonensis
• Grantee: Ismael Pretto Sauter
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/15254-8 - Involvement of CD200 in the infection of L. (L.) amazonensis isolates associated to cutaneous Leishmaniasis (LCL) and Difuse cutaneous Leishmaniasis (DCL)
• Grantee: Lina Borda Samper
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 16/08593-9 - Pan-Resistome of beta-lactamase (KPC-2, CTX-M-8, CTX-M-15)-producing Klebsiella pneumoniae and Escherichia coli isolates endemic in Brazil
• Grantee: Nilton Erbet Lincopan Huenuman
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/24105-3 - Immunobiology of Leishmania spp.: study of the role of CD200 and biogenesis of parasitophorous vacuole in fagocitic cells infected by Leishmania
• Grantee: Mauro Javier Cortez Véliz
• Support Opportunities: Research Grants - Young Investigators Grants