Is toxoplasmosis curable in humans -

Is toxoplasmosis curable in humans is toxoplasmosis curable in humans is toxoplasmosis curable in humans

For more than 50 years, the mainstay of treatment for acute toxoplasmosis humanns been a combination of a dihydrofolate reductase inhibitor and a sulfa antimicrobial. While this is currently a critical therapeutic strategy, currently approved drugs cannot eliminate latent parasites in cysts that are found in chronically infected individuals. Moreover, these drugs have significant bone marrow, are suspected teratogens and the emergence of resistance remains a potential threat to treatment.

Repurposing FDA-approved drugs will accelerate drug discovery for neglected parasitic diseases.

is toxoplasmosis curable in humans

Most recently, auranofin, a reprofiled drug that is FDA-approved for treatment of rheumatoid is toxoplasmosis curable in humans, has emerged as a promising anti-parasitic agent. It has antiproliferative activity against Plasmodium falciparum Sannella et al. Despite this promising broad spectrum ucrable anti-parasitic activity, the molecular target of auranofin has only been indirectly implicated as thioredoxin reductase.

Thioredoxin reductase enzymes are found in archaea, bacteria and diverse eukaryotes and play a key role in reduction of disulfide bonds that is essential for cell replication and survival. In humans, inhibition of thioredoxin reductase 1 induces expression of heme oxygenase-1 to repress inflammation Kobayashi et al. We previously demonstrated that auranofin reduces T. It is hypothesized that the anti-parasitic activity of auranofin comes from inhibition of the thioredoxin reductase enzyme of these parasites, akin to its action on human cells Kuntz et al.

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This postulated mechanism jn action explains why parasites treated with auranofin accumulate ROS Debnath et al. Intriguingly, auranofin may improve infection outcome is toxoplasmosis curable in humans decreasing pathogenic host inflammatory damage in addition to its direct inhibition of parasite replication. In this paper we describe our work to investigate resistance to auranofin in T. This approach illuminates mechanisms of resistance that might arise during its use as an anti-parasitic. In some circumstances, identification of resistance mechanisms validates proposed drug targets [i. In this study, we found that resistance was not associated with changes to the Toxoplasma thioredoxin reductase gene and no other single locus emerged as a consistent site underlying resistance.

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However, we observed that resistant clones accumulated less ROS than their wild type counterparts, demonstrating that auranofin resistance enhances oxidative stress responses. We will refer to this complete medium as D We mutagenized T. Briefly, approximately 1.

is toxoplasmosis curable in humans

These parasites were washed and transferred to a new confluent HFF monolayer for selection with auranofin 2. We selected ten representative T.]

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