UGA researchers find algal ancestor is key to how deadly pathogens proliferate

(Press-News.org) Athens, Ga. – Long ago, when life on Earth was in its infancy, a group of small single-celled algae propelled themselves through the vast prehistoric ocean by beating whip like tails called flagella. It's a relatively unremarkable tale, except that now, more than 800 million years later, these organisms have evolved into parasites that threaten human health, and their algal past in the ocean may be the key to stopping them.

The organisms are called apicomplexa, but people know them better as the parasites that cause malaria and toxoplasmosis, serious diseases that infect millions of people every year, particularly in the developing world.

Now, researchers at the University of Georgia have discovered how an important structure inside these parasitic cells, which evolved from the algal ancestor millions of years ago, allows the cells to replicate and spread inside their hosts. Their research may soon lead to new therapies to halt these deadly pathogens before they cause disease.

In order to survive, the parasitic apicomplexa must invade an animal or human and force its way into the cells of its host. Once inside the host cell, the parasite begins to replicate into numerous daughter cells that in turn create additional copies, spreading the infection throughout the body.

In their study, published Dec. 11 in PLoS Biology, the researchers demonstrate that, during the process of replication, the parasite cell loads genetic material into its daughter cells via a strand of fiber that connects the two. By altering the genes for the components of the fiber in the laboratory, the researchers discovered that they could prevent parasite replication, making the parasite essentially harmless.

"These altered parasites can initially infect cells, but once we turn off the fiber genes, they cannot create new daughter cells and spread," said Maria Francia, lead author and doctoral candidate in the department of cellular biology. "Since it cannot replicate, the parasite eventually dies without causing serious harm."

This replication fiber appears to have evolved from the flagellum that ancient algae used to swim.

"This was a surprising finding," said Boris Striepen, a Georgia Research Alliance Distinguished Investigator in UGA's Center for Tropical and Emerging Global Diseases. "These parasites no longer use flagella to swim, but they have apparently repurposed this machinery to now organize the assembly of an invasive cell."

During evolution, flagella have been reengineered to serve numerous different functions in animals, including the sensors that allow us to see and smell. This study suggests that in these parasites structures used to invade host cells may be also derived from flagella.

Current treatments for diseases like malaria are threatened by the parasite becoming resistant to the drugs, so the need for new therapies is always pressing.

This algae-based connective fiber may serve as a promising target for anti-parasitic drug development, said Striepen, who is also a cellular biologist in the Franklin College of Arts and Sciences. He cautions, however, that more work must be done to learn how to manipulate or destroy the fiber in parasites that have infected humans or animals.

But both Striepen and Francia argue that scientists do well to pay close attention to the evolutionary history of the organisms they study.

"It is extremely important to understand the evolution of different organisms, but especially the evolution of pathogens," Striepen said. "The analysis of their evolution produces important opportunities to develop treatments, but it also helps us understand the basic structure of the pathogens that we must fight."

### UGA Center for Tropical and Emerging Global Diseases The University of Georgia Center for Tropical and Emerging Global Diseases draws on a strong foundation of parasitology, immunology, cellular and molecular biology, biochemistry and genetics to develop medical and public health interventions for at-risk populations. Established in 1998, the center promotes international biomedical research and educational programs at UGA and throughout Georgia to address the parasitic and other tropical diseases that continue to threaten the health of people throughout the world. For more information about the center, see http://ctegd.uga.edu.

Writer: James Hataway, 706/542-5222, jhataway@uga.edu Contact: Boris Striepen, 706/583-0588, striepen@uga.edu