Development of Novel Drugs to Treat Amoebic Dysentery by Inhibition of Entamoeba histolytica MTA Nucleosidase
Additional Funding Sources
LL received support from the Pacific Northwest Louis Stokes Alliance for Minority Participation through the National Science Foundation grant #HRD-1410465. TS and LJM were the recipients of Ralph Jones Premedical Fellowships and INBRE Summer Research Fellowships at Boise State University. The project was supported by the Idaho Beef Council, by the National Institutes of Health (NIH) under Grant #1R15GM125065-01, and NIH program grants NIH/NIGMS P20GM103408 and P20GM109095. The project was also supported by The Biomolecular Research Center at Boise State University, and the Institute for Translational Health Sciences (ITHS).
Abstract
Entamoeba histolytica is an anaerobic intestinal parasite that causes amoebic dysentery, a disease that afflicts about 50 million people on the planet and is estimated to kill around 55,000 people per year. People living in tropical developing countries in Latin America, Asia, and Africa are at the highest risk of contracting the disease when they consume food or water contaminated with cysts that are passed in the feces. With few medications available to treat E. histolytica infections, it is important to develop novel drugs that target parasite specific processes. One such target is the enzyme Methylthioadenosine Nucleosidase (MTN), which the parasite uses to salvage important methionine and purine nutrients that it cannot make otherwise. In our work, we are examining new inhibitors that specifically target the parasite MTN enzyme in hopes of causing E. histolytica death by nutrient starvation. Most of our study is focused on examining the essential activity of the MTN enzyme, and measuring the degree of inhibition that is caused by several proposed MTN inhibitors that were previously identified by computer aided screening. The results of these studies set the stage to further explore MTN inhibitors as novel antiparasitic drugs to treat amoebic dysentery.
Development of Novel Drugs to Treat Amoebic Dysentery by Inhibition of Entamoeba histolytica MTA Nucleosidase
Entamoeba histolytica is an anaerobic intestinal parasite that causes amoebic dysentery, a disease that afflicts about 50 million people on the planet and is estimated to kill around 55,000 people per year. People living in tropical developing countries in Latin America, Asia, and Africa are at the highest risk of contracting the disease when they consume food or water contaminated with cysts that are passed in the feces. With few medications available to treat E. histolytica infections, it is important to develop novel drugs that target parasite specific processes. One such target is the enzyme Methylthioadenosine Nucleosidase (MTN), which the parasite uses to salvage important methionine and purine nutrients that it cannot make otherwise. In our work, we are examining new inhibitors that specifically target the parasite MTN enzyme in hopes of causing E. histolytica death by nutrient starvation. Most of our study is focused on examining the essential activity of the MTN enzyme, and measuring the degree of inhibition that is caused by several proposed MTN inhibitors that were previously identified by computer aided screening. The results of these studies set the stage to further explore MTN inhibitors as novel antiparasitic drugs to treat amoebic dysentery.
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