Widely used anti-bacterial inhibits parasites that cause malaria and toxoplasmosis
February 5, 2001
Triclosan, a common antiseptic used in household products such as toothpaste, skin creams, and deodorants, kills the parasites responsible for malaria and toxoplasmosis--even at very low concentrations, reports a team of researchers from the United States and the United Kingdom in the February issue of the International Journal for Parasitology.
Triclosan has been used as an antiseptic since the 1960s. It blocks an enzyme, known as "FabI," that bacteria need to manufacture the fatty acids used in cell membranes. Because animals possess a very different set of enzymes, triclosan does not interfere with this process in humans. This has led to its widespread use in over-the-counter preparations used on the skin or in the mouth.
“This common, inexpensive antimicrobial is remarkably effective against these parasites at concentrations that have no detectable toxicity,” said first author Rima McLeod, MD, the Jules and Doris Stein Research to Prevent Blindness Professor of Ophthalmology and Visual Sciences at the University of Chicago.
"That's good news because we urgently need new and better medicines to treat malaria and toxoplasmosis," she added. "The parasites that cause malaria are resistant to many of the available drugs, and there is no medication that affects the latent life-cycle stages of the parasite that causes toxoplasmosis."
"This finding gives us a blueprint to design an effective and safe new drug," said co-author Craig Roberts of the University of Strathclyde, UK."
Malaria affects more than 300 million people worldwide and kills an estimated 3,000 people, mostly children, each day. Although most cases originate in the tropics, there has been a steady increase in U.S. and European reports of "airport malaria" cases involving people who come down with the disease without ever visiting the tropics.
An estimated 30 percent of Americans are infected with the parasite, spread by cats, that causes toxoplasmosis. Although it is usually harmless, Toxoplasma gondii can cause devastating problems for those with weakened immune systems or when transmitted from mother to unborn child. About 3,000 infants are born each year in the U.S. with toxoplasmosis. The disease can cause severe eye damage, mental retardation, and death. The cost of caring for these children is estimated to exceed $500 million per year.
The parasites that cause these diseases are members of the phylum Apicomplexa. Three years ago, McLeod’s team discovered that the organisms in this phylum all shared genes for a plant-like metabolic pathway, and that the herbicide glyphosate ("Roundup") interfered with part of that pathway, inhibiting parasite growth and survival.
The current study shows that these parasites also have a FabI that was very similar to the bacterial or plant form of the enzyme, and that triclosan at low concentrations was extremely effective against these parasites in tissue culture, without harming the host cells. Triclosan was even effective against strains of the malarial parasite, Plasmodia falciparum, that had developed resistance to established anti-malarial medications noted co-authors Dennis Kyle and Wil Milhous from Walter Reed Army Institute of Research in Washington, DC.
"These findings may provide novel ways to counteract the increasing resistance of Plasmodia to the current armory of antimalarial agents and provide a new approach to the great need for additional, less toxic antimicrobial agents effective against toxoplasmosis," note the authors.
The researchers suggest that triclosan could be combined with other plant- and bacterial-enzyme inhibitors they are investigating to disrupt fatty acid synthesis at multiple points, a strategy that could prevent or delay the development of resistant microbes.
David Rice and John Rafferty are members of the Department of Molecular Biology and Biotechnology at the University of Sheffield and were key collaborators in this work. They have studied the structure of FabIs from plants and bacteria and found that the malarial enzyme is most similar to that from plants. The malarial FabI has the same pattern of critical amino acids that bind triclosan as the plant and bacterial variants.
Additional authors of the paper include Ernest Mui, Michael Kirisits and Douglas Mack from the University of Chicago; Benjamin Samuel from Northwestern University, in Chicago, and Stephen Muench from the University of Sheffield.
Funding support came from several sources including, from the US, the National Institutes of Health and Research to Prevent Blindness Foundation, and from the UK, the Wellcome Trust, the Biotechnology and Biological Sciences Research Council, and the Royal Society.
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