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New twist on potential malaria drug target acts by trapping parasites in cells
Date:5/14/2010

. 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."

Even better, the protein is found in the parasite and in plants, but not in humans, which means a drug targeted to that protein may be less toxic for people. The protein belongs to a family of Plasmodium falciparum calcium-dependent protein kinases, or PfCDPK5 for short in this case. Other members of the family have been implicated in parasite egress of red blood cells, but this is the first study using a genetic technique to validate a protein critical for parasite egress of red blood cells, according to the researchers.

Many companies and labs are looking for inhibitors of parasite egress and invasion of red blood cells, but no anti-malarial drugs yet target these stages of the parasite lifecycle, Dvorin said.

The paper also demonstrates the usefulness of a new tool that can be used to evaluate additional members of the kinase family, as well as other signaling pathways that regulate key events in the blood stage of malaria infection. As of 2002, "we have a malaria genome of about 6,000 genes," said Duraisingh. "We need a means of prioritizing specific gene candidates for further drug development." '/>"/>

Contact: Christina Roache
croache@hsph.harvard.edu
617-384-8979
Harvard School of Public Health
Source:Eurekalert

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