MANCHESTER/CAMBRIDGE, UK: Over half a million deaths per year result from malaria, caused by parasites of the genus Plasmodium, and with increasing resistance to all existing drugs, there is an urgent need to develop new medication. Approximately 90 per cent of these deaths are due to Plasmodium falciparum, the parasite responsible for the most severe forms of the disease. Researchers have now investigated triclosan—a simple antimicrobial agent commonly found in toothpastes—as a potential antimalarial substance.
Upon biting someone, a mosquito infected with malaria parasites transfers the parasites into the bloodstream via its saliva. These parasites travel to the liver, where they mature and reproduce, and later leave the liver and hijack red blood cells, where they continue to multiply, spreading around the body.
Triclosan in toothpaste prevents the build-up of plaque bacteria by inhibiting the action of an enzyme known as enoyl reductase (ENR), which is involved in the production of fatty acids. Triclosan and its analogues have been repeatedly shown to inhibit the growth of blood-stage P. falciparum in culture, and it was assumed that triclosan was targeting ENR, which is found in the liver. However, subsequent work showed that improving triclosan’s ability to target ENR had no effect on parasite growth in the blood.
Using “Eve”, an artificially intelligent “robot scientist” based at the University of Manchester’s School of Computer Science, the researchers, from the University of Cambridge, discovered that triclosan affects parasite growth by specifically inhibiting an enzyme of the malaria parasite, called dihydrofolate reductase (DHFR).
In a statement released by the University of Manchester, lead author Dr Elizabeth Bilsland said: “The discovery by our robot ‘colleague’ Eve that triclosan is effective against malaria 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.”
DHFR is the target of a well-established antimalarial drug, pyrimethamine; however, resistance to the drug among malaria parasites is common, particularly in Africa. The Cambridge team showed that triclosan was able to target and act on this enzyme even in pyrimethamine-resistant parasites.
The study, titled “Plasmodium dihydrofolate reductase is a second enzyme target for the antimalarial action of triclosan”, was published in the Scientific Reports journal on 18 January 2018.
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