Structure And Biosynthesis Of Entamoeba Histolytica Proteophosphoglycans

Funder

National Health and Medical Research Council

Funding Amount

$85,380.00

Summary

The intestinal parasite, Entamoeba histolytica is the cause of amoebic dysentry and liver abscess. It is the second most important parasitic disease after malaria, infecting 50 million people and causing 110 000 deaths annually. We have recently shown that the cell surface of infective stages of this parasite are coated by an unusual class of macromolecules called proteophosphoglycans (PPGs). These molecules appear to be major virulence factors, and the expression of PPGs with particular sugar m .... The intestinal parasite, Entamoeba histolytica is the cause of amoebic dysentry and liver abscess. It is the second most important parasitic disease after malaria, infecting 50 million people and causing 110 000 deaths annually. We have recently shown that the cell surface of infective stages of this parasite are coated by an unusual class of macromolecules called proteophosphoglycans (PPGs). These molecules appear to be major virulence factors, and the expression of PPGs with particular sugar modifications is associated with highly pathogenic strains. This proposal aims to determine the precise structure of the PPGs and to define functionally important domains in these molecules. We will also investigate how these molecules are assembled and processed in the parasite. In particular, we aim to characterize enzymes that generate PPG structures only found in virulent strains of Entamoeba histolytica. Assays will be established for these enzymes which will allow us to screen for inhibitors that may be used as potential anti-amoebic drugs. These studies will provide insights into the surface chemistry of these important human parasites and identify new drug targets.
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