Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/20089
Title: Silver and Nitrate Oppositely Modulate Antimony Susceptibility through Aquaglyceroporin 1 in Leishmania (Viannia) Species
Authors: Andrade, Juvana Moreira
Baba, Elio Hideo
Avila, Ricardo Andrez Machado de
Olortegui, Carlos Chavez
Demicheli, Cynthia Peres
Frézard, Frédéric
Monte Neto, Rubens Lima do
Murta, Silvane Maria Fonseca
Affilliation: Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
Universidade do Extremo Sul Catarinense. Unidade Acadêmica de Ciências da Saúde. Criciúma, SC, Brazil/Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciências Exatas. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
Abstract: Antimony (Sb) resistance in leishmaniasis chemotherapy has become one of the major challenges to the control of this spreading worldwide public health problem. Since the plasma membrane pore-forming protein aquaglyceroporin 1 (AQP1) is the major route of Sb uptake in Leishmania, functional studies are relevant to characterize drug transport pathways in the parasite. We generated AQP1-overexpressing Leishmania guyanensis and L. braziliensis mutants and investigated their susceptibility to the trivalent form of Sb (SbIII) in the presence of silver and nitrate salts. Both AQP1-overexpressing lines presented 3- to 4-fold increased AQP1 expression levels compared with those of their untransfected counterparts, leading to an increased SbIII susceptibility of about 2-fold. Competition assays using silver nitrate, silver sulfadiazine, or silver acetate prior to SbIII exposure increased parasite growth, especially in AQP1-overexpressing mutants. Surprisingly, SbIII-sodium nitrate or SbIII-potassium nitrate combinations showed significantly enhanced antileishmanial activities compared to those of SbIII alone, especially against AQP1-overexpressing mutants, suggesting a putative nitrate-dependent modulation of AQP1 activity. The intracellular level of antimony quantified by graphite furnace atomic absorption spectrometry showed that the concomitant exposure to SbIII and nitrate favors antimony accumulation in the parasite, increasing the toxicity of the drug and culminating with parasite death. This is the first report showing evidence of AQP1-mediated SbIII susceptibility modulation by silver in Leishmania and suggests the potential antileishmanial activity of the combination of nitrate salts and SbIII.
Keywords: Leishmaniasis
Leishmania guyanensis
L. braziliensis
keywords: Leishmanioses
Issue Date: 2016
Publisher: American Society for Microbiology
Citation: ANDRADE, Juvana Moreira et al. Silver and Nitrate Oppositely Modulate Antimony Susceptibility through Aquaglyceroporin 1 in Leishmania (Viannia) Species. Antimicrob Agents Chemother, v. 60, n. 8, p. 4482–4489, 2016
DOI: 10.1128/AAC.00768-16
ISSN: 0066-4804
Copyright: restricted access
Appears in Collections:IRR - Artigos de Periódicos

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