Harvard School of Public Health (HSPH) researchers and colleagues seeking to block invasion of healthy red blood cells by malaria parasites have instead succeeded in locking the parasites within infected blood cells, potentially containing the disease.
The findings reveal an essential step in the biology of the most common and severe malaria parasite, Plasmodium falciparum, and offer a new drug target for fighting one of the world's most common and dangerous infections.
Malaria sickens up to one half billion people every year and kills up to one million, mostly children in sub-Saharan Africa. The high fevers, shaking chills, flu-like symptoms, and anemia can be fatal unless treated quickly. Malaria has grown resistant to a long list of drugs, and vaccines are still in experimental stages.
Working with the malaria parasite and human blood in test tubes and lab dishes, the research team identified a single fast-acting protein in the parasite that enables it and several dozen of its offspring to escape from a human red blood cell in preparation for quick invasion of many more healthy blood cells. Eliminating that protein traps the parasites in the cell.
After an infected mosquito bites a person, malaria parasites move into the liver, where they silently mature and multiply within weeks. Malaria parasites make people sick weeks or months later when they enter red blood cells and begin an exponential expansion. In a single cell, a parasite produces up to 32 offspring in about two days, which burst out to infect more red blood cells.
"This is the stage where things have to happen very fast for the parasite," said senior author Manoj Duraisingh, HSPH assistant professor of immunology and infectious diseases and senior author of the paper in the May 14 Science. "The parasite doesn't like to spend much time outside the cell. It grows and matures, and immediately following rupture, enters a new cell. It was a surprise that this protein kinase, which we thought would be involved in red blood cell invasion, turns out to be essential for the parasite getting out of the cell."
The study helps define the exit of the parasite from a blood cell as a highly choreographed process and distinguishes the egress and invasion steps, the researchers said.
"When the parasite gets out of the red blood cell, it has a matter of seconds or minutes to get into new red blood cells, or it will be cleared or killed by the human immune system," said first author Jeffrey Dvorin, a postdoctoral research fellow in the Duraisingh Lab at HSPH and a clinical fellow in pediatric infectious diseases at Children's Hospital Boston. "We found an important trigger for the parasite to exit cells that may be independent from the invasion trigger
http://www.sciencedaily.com/releases/2010/05/100514171912.htm
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