An artificially intelligent robot has helped to discover that an ingredient in toothpaste could be used as an anti-malarial drug, British researchers have reported.
Eve, the AI robot, assisted researchers at the University of Cambridge, England, in high-throughput screening.
This showed that triclosan, an ingredient found in many toothpastes, may help the fight against drug-resistance in strains of a malaria parasite that have grown resistant to one of the currently-used drugs.
When used in toothpaste, triclosan 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.
Although it is already known that triclosan, which prevents the build-up of plaque bacteria by inhibiting enoyl reductase (ENR), also inhibits the growth in culture of the malaria parasite Plasmodium during the blood-stage, it was demonstrated that improving triclosan’s ability to target ENR had no effect on parasite growth in the blood.
Working with ‘Eve’, the research team discovered triclosan affects parasite growth by specifically inhibiting DHFR, a different enzyme of the malaria parasite.
DHFR is the target of pyrimethamine, a well-established antimalarial drug, but resistance to the drug among malaria parasites is common.
The researchers report that triclosan could target and act on this enzyme even in pyrimethamine-resistant parasites.
Professor Steve Oliver, of the Cambridge Systems Biology Centre and the Department of Biochemistry at the University of Cambridge, said: “Drug-resistant malaria is becoming an increasingly significant threat in Africa and south-east Asia, and our medicine chest of effective treatments is slowly depleting. The search for new medicines is becoming increasingly urgent.”
Because triclosan inhibits both ENR and DHFR, the researchers, writing in Scientific Reports, say it may be possible to target the parasite at both the liver stage and the later blood stage
Eve was developed by a team of scientists at the Universities of Manchester, Aberystwyth, and Cambridge to automate the drug discovery process.
It automatically develops and tests hypotheses to explain observations, run experiments using laboratory robotics, interpret the results to amend their hypotheses, and then repeat the cycle, automating high-throughput hypothesis-led research.
Bilsland, E et al. Plasmodium dihydrofolate reductase is a second enzyme target for the antimalarial action of triclosan. Scientific Reports 18 January 2018; doi: 10.1038/s41598-018-19549-x
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