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How Montezuma gets his revenge
Date:6/14/2008

Every year, about 500 million people worldwide are infected with the parasite that causes dysentery, a global medical burden that among infectious diseases is second only to malaria. In a new study appearing in the June 15 issue of Genes and Development, Johns Hopkins researchers may have found a way to ease this burden by discovering a new enzyme that may help the dysentery-causing amoeba evade the immune system.

"This is the first enzyme to be identified that looks like it could mediate immune system evasion," says Sin Urban, Ph.D., an assistant professor of molecular biology and genetics at Hopkins.

The EhROM1 enzyme, it turns out, is part of an ancient group of enzymesthey are found in every branch of life from bacteria to manknown as rhomboid enzymes. In most animals, rhomboid enzymes seem to play a role in cell-to-cell communication, but a couple of years ago Urban found that malaria parasites use rhomboid enzymes for a more sinister purpose: to enter host cells uninvited.

That led his team to scour the DNA of other parasites to see if any of them also had genes that encode rhomboid enzymes. They found that the dysentery-causing amoeba Entamoeba histolytica contains one rhomboid enzyme and named it EhROM1.

"Plasmodia, the parasites that cause malaria, grab onto a host cell and push their way in," explains Urban. "Once inside they use rhomboid enzymes to cut themselves loose." But amoebas don't enter cells to cause dysentery, so Urban's team set out to figure out how these parasites use EhROM1.

They first identified protein targets cut by EhROM1 by looking for amoeba proteins that had structural signatures similar to those cut by malaria rhomboids. They found these signatures in a family of proteinslectinsthat are found on cell surfaces. The researchers put both proteins into cells and verified that EhROM1 does cut one particular lectin, and the more EhROM1 they added, the more lectin pieces resulted
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Contact: Audrey Huang
audrey@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
Source:Eurekalert

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