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January 18, 2018

Robot Scientist Uncovers How Common Antibacterial Kills Drug-Resistant Malaria

A malaria-infected red blood cell [NIH]

  • Legendary thinkers and technology savvy individuals such as Stephen Hawking and Elon Musk have rightfully cautioned against the rapid development and overreliance on artificial intelligence (AI). Yet, there is an upside, as a team of investigators led by scientists at the University of Cambridge have just discovered. The UK team employed a robotic scientist named Eve for a high-throughput screen and discovered that triclosan, an antibacterial ingredient, “which is safe enough to be incorporated into consumer products from toothpaste to toys,” may help the fight against drug-resistant malaria. Findings from the new study were published today in Scientific Reports, in an article entitled “Plasmodium Dihydrofolate Reductase Is a Second Enzyme Target for the Antimalarial Action of Triclosan.”        

    "Drug-resistant malaria is becoming an increasingly significant threat in Africa and Southeast Asia, and our medicine chest of effective treatments is slowly depleting," explained senior study investigator Stephen Oliver, Ph.D., professor in the department of biochemistry at the University of Cambridge and the Cambridge Systems Biology Centre. "The search for new medicines is becoming increasingly urgent."  

    Triclosan has been shown previously to prevent the buildup of plaque bacteria by inhibiting the action of an enzyme known as enoyl reductase (ENR), which is involved in the production of fatty acids. Scientists have known for some time that triclosan also inhibits the growth in culture of malaria parasites during the blood stage, and assumed that this was because it was targeting ENR, which is found in the liver. However, subsequent work showed that improving triclosan's ability to target ENR did not affect parasite growth in the blood.

    Working with Eve, the research team discovered that, in fact, triclosan affects parasite growth by specifically inhibiting an entirely different enzyme of the malaria parasite, called dihydrofolate reductase, or DHFR. DHFR is the target of a well-established antimalarial drug, pyrimethamine. However, resistance to pyrimethamine among malaria parasites is common, particularly in Africa. Amazingly, the Cambridge team showed that triclosan was able to target and act on this enzyme even in pyrimethamine-resistant parasites. Because triclosan inhibits both ENR and DHFR, the investigators suggest it may be possible to target the parasite at both the liver stage and the later blood stage.

    "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,” remarked lead study investigator Elizabeth Bilsland, Ph.D., assistant professor at the University of Campinas, Brazil. “We know it is a safe compound, and its ability to target two points in the malaria parasite's life cycle means the parasite will find it difficult to evolve resistance."

    Eve was developed by a team of scientists at the Universities of Manchester, Aberystwyth, and Cambridge to automate—and hence 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 then repeat the cycle, automating high-throughput hypothesis-led research.

    "Artificial intelligence and machine learning enable us to create automated scientists that do not just take a 'brute force' approach, but rather take an intelligent approach to science,” concluded co-senior study investigator Ross King, Ph.D., a professor at the Manchester Institute of Biotechnology, who led the development of Eve. “This could greatly speed up the drug discovery progress and potentially reap huge rewards."

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