CLEMSON — Kerry Smith’s research may help the health of millions of people around the globe.

Smith, an associate professor in the Clemson University genetics and biochemistry department, has been awarded grants from the National Science Foundation and the National Institutes of Health totaling nearly $950,000. The money will be used to investigate biochemical pathways found in certain disease-causing eukaryotic microbes, including the fungus Cryptococcus neoformans and the single-celled protozoan Entamoeba histolytica. One is connected with fungal meningitis, the other with amoebic dysentery.

Smith’s work deals with how some simple forms of life make and regulate energy. Regardless of size, all living cells must have fuel to thrive and reproduce.

Working with one-celled organisms makes it easier for scientists like Smith to study metabolism — the processes that control growth and energy uptake — and to conduct experiments by altering the microbes and their abilities to absorb food and utilize nutrients. Smith’s results provide new insights into enzymes, which are proteins that increase the rate of specific biochemical reactions, and the metabolic processes they control.

According to Smith’s research, the enzyme acetate kinase was previously thought to be present only in bacteria and one other type of prokaryote (simple one-celled life forms lacking internal structures), but the Smith lab recently identified this important metabolic enzyme in a number of eukaryotic (cells with complex internal structures, such as a nucleus) microbes.

The specific aims of these projects are to understand the basis for the biochemical differences among the eukaryotic and bacterial acetate kinases and to determine the physiological roles of this enzyme in fungi and single-celled microorganisms, including partner enzymes that work with acetate kinase to form metabolic pathways.

Cheryl Ingram-Smith, a research assistant professor and an expert in acetate kinase enzymology, and Indi Bose, an assistant professor at Western Carolina University and an expert in Cryptococcus molecular biology, are co-principal investigators.

The Smith lab is studying acetate kinase from several microbes. The first is a methane-producing microbe in which this enzyme catalyzes the first step in the production of methane, a greenhouse gas. Smith and his colleagues also are studying the role of this enzyme in the fungus Cryptococcus neoformans. A yeast, C. neoformans is a dangerous life form. An infection with C. neoformans, called cryptococcosis, causes fungal meningitis, which can cause severe problems for AIDS patients, but is rare in people with healthy immune systems.

The researchers are especially interested in Entamoeba histolytica, a parasitic protozoan (one-celled microorganism) that infects humans and other primates. E. histolytica is estimated to infect about 50 million people worldwide. It causes an infection that can lead to amoebic dysentery or amoebic liver abscesses. Symptoms can include dysentery, bloody diarrhea, weight loss, fatigue and abdominal pain. The amoeba can burrow into the intestinal wall and it may reach the blood stream. From there, it can reach different vital organs of the human body, usually the liver, but sometimes the lungs, brain, spleen or other organs. A common outcome is a liver abscess, which can be fatal if untreated.

The interest in acetate kinase lies in the fact that this enzyme, while found in bacteria and certain disease-causing eukaryotic microbes, is not present in humans or animals. This makes acetate kinase a potential target for development of antibiotics that would target the microbe but would not have an effect on the human host. First, however, research must determine the exact role of acetate kinase in these microbes and whether the enzyme is necessary for cell growth or infection.

The research Smith and his colleagues are doing will not only advance scientific understanding of how energy in some microorganisms is regulated, but also how to disrupt the process, and could lead to new medicines.

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