Abstract
Toxoplasmosis is a common parasitic disease caused by Toxoplasma gondii (Nicolle et Manceaux, 1908), an obligate parasite capable of infecting a range of cell types in almost all warm-blooded animals. Upon infecting an intermediate host, the parasites differentiate into tachyzoites which rapidly infect host tissues. Usually, the invading parasites are cleared by the immune system and administered drugs, but some tachyzoites differentiate into bradyzoites forming tissue cysts. These tissue cysts could serve as a source for re-infection and exacerbations. Currently, treatment for toxoplasmosis is limited and, moreover, there are no drugs for treating the cystic stage thus rendering toxoplasmosis a global burden. Recently, we demonstrated that inorganic nanoparticles showed promising activity against the tachyzoite stage T. gondii. In the present study, we evaluated nanoparticles for effect on bradyzoite formation in vitro. Data revealed that the nanoparticles limited bradyzoite burden in vitro. Further, the nanoparticles decreased the bradyzoite-specific BAG-1 promoter activity relative to the untreated control under a bradyzoite-inducing culture condition, even though this reduction in BAG-1 promoter activity waned with increasing concentrations of nanoparticles. In contrast, a parallel experiment under normal cell culture conditions showed that the nanoparticle treatment mildly increased the BAG-1 promoter activity relative to the untreated control. Taken together, the findings are evidence that nanoparticles not only possess anti-tachyzoite potential but they also have anti-bradyzoite potential in vitro.
Highlights
Toxoplasma gondii (Nicolle et Manceaux, 1908) is the causative agent of toxoplasmosis, which affects nearly one-third of the human population (Black and Boothroyd 2000)
Under the second experimental condition, we found that the NPs significantly reduced parasite cyst wall formation in vitro (Fig. 1B)
The large global burden of toxoplasmosis and the lack of effective therapeutic options underscore the urgent need for better anti-T. gondii drugs
Summary
Toxoplasma gondii (Nicolle et Manceaux, 1908) is the causative agent of toxoplasmosis, which affects nearly one-third of the human population (Black and Boothroyd 2000). The parasite transits between the tachyzoite and bradyzoite (cystic) forms, making the life cycle complex (Black and Boothroyd 2000). The small size and large ratio of surface area to volume are unique characteristics of nanoparticles, which can be exploited for medicinal value These properties enhance reactivity and aids easy cellular penetration which might result in interaction with cellular biomolecules in a number of ways (Adeyemi et al 2017). We recently showed that inorganic nanoparticles have strong activity against the tachyzoites form of T. gondii in vitro and these nanoparticles significantly suppressed parasite growth by ≥ 80% possibly through generation of reactive oxygen species (Adeyemi et al 2017). We sought to determine whether nanoparticles can prevent and/or eliminate the cystic forms of T. gondii in vitro
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