Newswise — Researchers have succeeded in sequencing the genome of a parasitic amoeba called Entamoeba histolytica. The amoeba infects about 50 million people around the world with a disease called amebiasis, causing up to 100,000 deaths a year, usually in developing countries with poor sanitary conditions. The researchers' work appears in the Feb. 24 issue of the journal Nature. It is the first genome-wide study of an amoeba and the first sequence to be published from a specific class of human pathogen. Four infectious disease experts from the University of Virginia Health System joined over forty scientists from the U.S., Europe and India in sequencing the E. histolytica genome. Their research is expected to help in the development of new vaccines and diagnostic tests that can distinguish the amoeba's deadliest strains.
Amebiasis is second only to malaria as a cause of death and disability from a parasite. The symptoms are often quite mild, according to the U.S. Centers for Disease Control and Prevention, and can include loose stools, stomach pain, and stomach cramping. Amebic dysentery is a severe form of amebiasis associated with stomach pain, bloody stools, and fever.
"Every aspect of research into disease is changed by having the genome sequenced," said study collaborator Dr. William A. Petri, Jr., head of the division of infectious diseases and international medicine at the U.Va. Health System. "The biochemical pathways by which the amoeba uses food for energy and metabolism are now known. Many of these pathways can now be targeted with inhibitors that could form new drug therapies for patients infected with E. histolytica."
Petri said the DNA typing from the genome sequenced is allowing the development of "new diagnostic tests that help distinguish the most deadly substrains of the parasite." The data will also help researchers find more about what makes some people innately resistant to infection and which acquired immune responses can protect people from re-infection, Petri said.
Barbara Mann, PhD, associate professor of internal medicine and microbiology at U.Va., was instrumental in persuading scientists from around the world to get involved in the project to unravel the E. histolytica genome, which was eventually led by The Institute for Genome Research (TIGR) in Rockville, Md., and the Wellcome Trust Sanger Institute in the U.K. Mann was also instrumental in securing funding for the genome project from the National Institute of Allergy and Infectious Diseases. "This research will have broad implications in helping us understand how this organism specifically causes disease," Mann said.
According to the Nature article, the genome sequence of E. histolytica includes a complex repertoire of sensory genes and a variety of bacterial-like genes that contribute to its unique biology. Scientists report evidence in the DNA sequence that E. histolytica likely picked up a significant number of its metabolic genes from bacterial co-inhabitants of the human gut. Scientists also found ample evidence of a variety of gene families characteristic of more complex organisms. A family of membrane receptors appears to be one of the mechanisms by which the parasite senses the presence of its human host and translates environmental cues into signaling events, which are processed by the parasite.
"Clearly, this amoeba has genes that allow it to sense certain facets of its environment and respond to those cues," said Neil Hall, a TIGR scientist who is the senior author of the Nature study. Matthew Berriman of Sanger said, "The results give a fascinating glimpse of how this ancient parasite evolved and highlight unusual metabolic processes that may be exploitable as drug targets."
The project identified some large families of surface proteins that may help mediate the amoeba's ability to evade the human immune system. This could explain why the parasite can stay hidden in the body for years at a time. The information may help researchers find better ways to harness the immune system to eradicate infection through vaccine development.
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