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EFFECT OF 3-BROMOPYRUVATE AND ATOVAQUONE ON INFECTION DURING IN VITRO INTERACTION OF TOXOPLASMA GONDII AND LLC-MK2 CELLS
3-Bromopyruvate
Atovaquone
LLC-MK2 Cells
In Vitro Interaction
Afiliación
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Estrutural. Rio de Janeiro, RJ, Brasil / Centro Universitário Estadual da Zona Oeste (UEZO). Laboratório de Tecnologia em Bioquímica e Microscopia. Campo Grande, RJ, Brasil.
Centro Universitário Estadual da Zona Oeste (UEZO). Laboratório de Tecnologia em Bioquímica e Microscopia. Campo Grande, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Estrutural. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Estrutural. Rio de Janeiro, RJ, Brasil.
Centro Universitário Estadual da Zona Oeste (UEZO). Laboratório de Tecnologia em Bioquímica e Microscopia. Campo Grande, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Estrutural. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Estrutural. Rio de Janeiro, RJ, Brasil.
Resumen en ingles
Toxoplasma gondii infection can be severe during pregnancy and in immunocompromised patients. Current therapies for toxoplasmosis
are restricted to tachyzoites and have little or no effect on bradyzoites, which are maintained in tissue cysts. Consequently,
new therapeutic alternatives have been proposed as the use of atovaquone has demonstrated partial efficacy against
tachyzoites and bradyzoites. This work studies the effect of 3-bromopyruvate (3-BrPA), a compound that is being tested against
cancer cells, on the infection of LLC-MK2 cells with T. gondii tachyzoites, RH strain. No effect of 3-BrPA on host cell proliferation
or viability was observed, but it inhibited the proliferation of T. gondii. The incubation of cultures with lectin Dolichos bi-
florus agglutinin (DBA) showed the development of cystogenesis, and an ultrastructural analysis of parasite intracellular development
confirmed morphological characteristics commonly found in tissue cysts. Moreover, the presence of degraded parasites
and the influence of 3-BrPA on endodyogeny were observed. Infected cultures were alternatively treated with a combination of
this compound plus atovaquone. This resulted in a 73% reduction in intracellular parasites after 24 h of treatment and a 71%
reduction after 48 h; cyst wall formation did not occur in these cultures. Therefore, we conclude that the use of 3-BrPA may serve
as an important tool for the study of (i) in vitro cystogenesis; (ii) parasite metabolism, requiring a deeper understanding of the
target of action of this compound on T. gondii; (iii) the alternative parasite metabolic pathways; and (iv) the molecular/cellular
mechanisms that trigger parasite death.
Palabras clave en ingles
Toxoplasma gondii3-Bromopyruvate
Atovaquone
LLC-MK2 Cells
In Vitro Interaction
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