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Compound Found In Toothpaste To Fight Drug-Resistant Malarial Infections
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Compound Found In Toothpaste To Fight Drug-Resistant Malarial Infections

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Highlights:
  • Triclosan, a compound found in toothpaste, could be used as an anti-malarial drug to target malarial parasite strains that are resistant to currently used drug pyrimethamine.
  • In toothpastes, triclosan prevents the build-up of plaque bacteria by inhibiting enoyl reductase (ENR), an enzyme involved in the production of fatty acids.
  • Triclosan inhibits two enzymes (ENR and DHFR) in the malarial parasite,, making it possible to target the parasite at both the liver stage and the later blood stage.

Triclosan, a commonly found ingredient in toothpaste could be used as an antimalarial drug to target malarial parasites that are resistant to currently used drugs, suggests a study by the University of Cambridge. By using Eve, an artificially-intelligent 'robot scientist' in a high-throughput screen the team discovered that triclosan, may help the fight against pyrimethamine-resistant parasite strains. The study is published in the journal Scientific Reports.

Malarial infection:

When a malarial parasite infected mosquito bites someone, the parasites are transferred into the host's bloodstream. Once, in the bloodstream, the parasites work their way to the liver where they mature and reproduce, called the liver stage of infection. Later, they leave the liver and attack red blood cells continuing to grow and reproduce, called the blood stage of infection. It is during this stage that the symptoms are seen and could eventually lead to life threatening conditions.

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While we do have drugs that are used to treat malaria, the parasites are growing resistant to currently available drugs at an alarming rate; this can alarmingly increase the cases of untreatable malaria in the future.

Triclosan: The new hope:

Commonly found in toothpastes, triclosan prevents the build-up of plaque by inhibiting enoyl reductase (ENR), an enzyme involved in the production of fatty acids.
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While it was previously found that triclosan inhibits the malaria parasite Plasmodium's growth in culture during the parasite's blood-stage, it was assumed that this was because it targeted ENR found in the liver. However, when triclosan's ability to target ENR was improved, it had no effect on the parasite's growth in blood.

The new study working with 'Eve' has discovered that triclosan affects parasite growth by specifically inhibiting an entirely different enzyme of the malaria parasite, known as dihydrofolate reductase or DHFR.

Pyrimethamine, a well-established anti-malarial drug, also targets the very same DHFR. However, the use of the drug is seemingly dropping as resistance to the drug among malaria parasites is common, particularly in Africa. But the good news is that triclosan was able to target and act on DHFR even in pyrimethamine-resistant parasites.

Moreover, since triclosan inhibits both ENR and DHFR, it is possible to target the parasite at both the liver stage and the later blood stage.

Lead author, Dr Elizabeth Bilsland, adds: "The discovery by our robot 'colleague' Eve that triclosan is effective against malarial targets offers hope that we may be able to use it to develop a new drug. We know it is a safe compound, and its ability to target two points in the malaria parasite's lifecycle means the parasite will find it difficult to evolve resistance."

References :
  1. AI 'scientist' finds that toothpaste ingredient may help fight drug-resistant malaria - (https://www.eurekalert.org/emb_releases/2018-01/uoc-af011718.php)
Source: Medindia

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