When used in toothpaste, triclosan prevents the buildup of plaque bacteria by inhibiting the action of an enzyme known as enoyl reductase (ENS), which is involved in the production of fatty acids. Now, it also may be used as an anti-malarial drug against strains of a malaria parasite that have grown resistant to a currently used drug, report researchers at the University of Cambridge.
When mosquitos infected with malaria parasites bite human beings, they transfer the parasites into the human bloodstream via their saliva. Once they reach the liver, these parasites mature and reproduce. A few days later, they leave the liver and hijack red blood cells, where they continue to multiply and spread throughout the body. Symptoms including potentially life-threatening complications then follow.
Scientists have known that triclosan inhibits the growth of the blood stage of the malaria parasite, Plasmodium, in culture. They assumed it did so because it was targeting ENR, which is essential for the growth of the parasite in the liver. However, subsequent work has shown that improving triclosan’s ability to target ENR has no effect on parasite growth in the blood.
Working with an artificially intelligent “robot scientist” known as Eve at the University of Manchester, the researchers found that triclosan affects parasite growth specifically by inhibiting an entirely different enzyme of the malaria parasite called DHFR. This means that triclosan may be able to target the parasite both at the liver stage and at the later blood stage.
Eve was developed by scientists from the universities of Manchester, Aberystwyth, and Cambridge to automate and speed up the drug discovery process by automatically developing and testing hypotheses to explain observations, run experiments using laboratory robotics, interpret the results to amend their hypotheses, and repeat the cycle, automating high-throughput hypothesis-led research.
“Artificial intelligence and machine learning enables us to create automated scientists that do not just take a ‘brute force’ approach, but rather take an intelligent approach to science,” said Ross King, PhD, a professor at the Manchester Institute of Biotechnology who led Eve’s development. “This could greatly speed up the drug discovery process and potentially reap huge rewards.”
DHFR is the target of a well-established antimalarial drug, pyrimethamine. Resistance to the drug among malaria parasites is common, though, particularly in Africa. The researchers showed that triclosan was able to target and act on this enzyme even in pyrimethamine-resistant parasites.
“Drug-resistant malaria is becoming an increasingly significant threat in Africa and southeast Asia, and our medicine chest of effective treatments is slowly depleting,” said Steve Oliver, PhD, of the Cambridge Systems Biology Centre and the Department of Biochemistry at the University of Cambridge. “The search for new medicines is becoming increasingly urgent.”
“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,” said lead author Elizabeth Bilsland, PhD, now an assistant professor at the University of Campinas. “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.”
The study, “Plasmodium Dihydrofolate Reductase Is a Second Enzyme Target for the Antimalarial Action of Triclosan,” was published by Scientific Reports.