Daniel J Eichinger PhD, Associate Professor

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Entamoeba parasites infect up to 50 million people annually, and cause 100,000 deaths. The parasite’s life cycle consists of the disease-causing trophozoite stage and the infectious cyst stage. The latter is acquired by ingestion of contaminated food or water, and multiplication and differentiation of the emergent tropohozoites occurs in the large intestine. Our lab studies the conditions within the large intestine that regulate the cyst formation process. Recently we have determined that amoeba trophozoites monitor the integrity of the mucus layer overlying the colonic epithelium using a cell surface lectin that binds to mucin. As the trophozoite cell density increases in a given location within the colon, the accompanying decrease in the mucin content is sensed as a clustering of the lectin on the cell surface, which induces aggregation of trophozoites and the release of signaling molecules. The trophozoites in the aggregates are responsive to exogenous bioactive amines, such as epinephrine, serotonin, and histamine. Each of these appears to be bound by a discrete receptor on the trophozoites, at least one of which is coupled to production of cAMP via G proteins.

Another mechanism that regulates the formation of cysts is the level of some fermentation products made by the normal bacterial population of the colon. Certain bacterial species produce large amounts of the short chain fatty acids (SCFA) acetate, propionate and butyrate, the latter of which has been demonstrated to inhibit histone deacetylase (HDAC) activity in higher eukaryotes. Entamoeba trophozoites, then, multiply in the colon of infected hosts in the presence of a defined HDAC inhibitor. We found that physiologic levels of SCFA did not interfere with trophozoite growth, but did inhibit differentiation of trophozoites into cysts. Encystment will occur, however, if SCFA levels are decreased 5-10 fold, again suggesting that the parasite can sense a change in the chemical composition of the mucus layer in which it resides. We have also determined that Entamoebae have an unusually large number of potential acetyl group modification sites on their histones, and that most of these are taken advantage of by trophozoites. Current studies are aimed at a more complete understanding of how the lectin, bioactive amine receptors, and SCFA/HDAC function to regulate the production of the infectious cyst stage of the parasite.

Selected Publications

1. Turner N, Eichinger, D. Entamoeba invadens: the requirement for galactose ligands during encystment. Exp. Parasitology 2007 Aug;116(4):467-74. Epub 2007 Mar 6.
2. Teixeira, M.C.A., Oliveira, G.G.S., Silvany, M.A., Alcantara-Nueves, N.M., Soares, M.B.P., Ribeiro-dos-Santos, R., Jeronimo, S.M.B., Costa, C.H., dos-Santos, W.L.C., Eichinger, D., Pontes-de-Carvalho, L. 2006. A strategy for identifying serodiagnostically relevant antigens of Leishmania or other pathogens in genetic libraries. Biologicals. 2007 Mar:35(1);51-4.
3. Ehrenkaufer GM, Haque R, Hackney JA, Eichinger DJ, Singh U. Identification of developmentally regulated genes in Entamoeba histolytica: insights into mechanisms of stage conversion in a protozoan parasites. Cell Microbiol. 2007 Jan 22 [Epub ahead of print].
4. Byers, J. and Eichinger, D. Entamoeba invadens: restriction of ploidy by colonic short chain fatty acids. Exp Parasitol. 2005 Jul;110(3):203-6.
5. Byers, J., Faigle, W., Eichinger D. Colonic short-chain fatty acids inhibit encystation of Entamoeba invadens. Cell Microbiol. 2005 Feb;7(2):269-79.
6. Frederick, J., D. Eichinger. Entamoeba invadens contains the components of a classical adrenergic signaling system. Mol. Biochem. Parasitol. 2001;137:339-343. (#J50635)
7. Wang, Z., J. Samuelson, C. G. Clark, D. Eichinger, J. Paul, K. Van Dellen, N. Hall, I. Anderson, B. Loftus. Gene discovery in the Entamoeba invadens genome. Mol. Biochem. Parasitol. 2003;129: 23-31. (#J45931)
8. D. Eichinger, A. Coppi, J. Frederick, and S. Merali. Catecholamines in Entamoebae: recent (re)discoveries. J. Biosci. 2002;27:589-593. (#J54058)
9. Coppi, A., S. Merali, D. Eichinger. The enteric parasite Entamoeba uses an autocrine catecholamine system during differentiation into the infectious cyst stage. J. Biol. Chem. 2002;277:8083-8090. (#J28980)
10. D. Eichinger. Encystation in parasitic protozoa. Cur. Opin. Microbiol. 2001; 4:421 426.