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T. gondii: The Movie

By Susan Muaddi Darraj

Glowing an unnatural emerald green, the oval-shaped parasite glides along the surface of its prey. After locating a prime space, the parasite binds itself to the cell and then pushes into its membrane. Once inside, it begins to replicate rapidly, feeding off its host and doubling every six hours.

Within two days, the single Toxoplasma gondii (T. gondii) parasite yields as many as 128 “daughter cells” that destroy their host cell and burst forth to invade others. It’s a textbook parasite invasion like any other, except this drama unfolds in front of a digital camera that snaps pictures every half-second, essentially creating a movie of T. gondii’s conquest. Using knowledge of the parasite gained by such methods, Vern Carruthers, PhD, assistant professor of Molecular Microbiology and Immunology, and his team have scored a recent breakthrough that may lead to drug treatments that will reduce this microscopic family’s ability to spread and infect humans.

Scientists estimate that nearly one-quarter of the world’s adult population is infected with the Toxoplasma parasite (spread most commonly through the consumption of infected, undercooked meat). The mild form of toxoplasmosis, the disease caused by T. gondii, may result in flu-like muscle aches, but people with healthy immune systems usually show no symptoms. Its severe form can cause eye or brain damage.

Carruthers and his team have been able to disrupt a protein that binds Toxoplasma to its host cell. “We knocked out a gene that encodes that protein, impairing the parasite’s ability to invade,” he explains. “We also restored the gene, which repaired its ability to invade —so now we’re sure this gene is responsible for disrupting the invasion.” Carruthers and his team are currently preparing a research paper on their discovery.

To simplify the observation of T. gondii’s invasion, Carruthers, along with PhD students Susannah Brydges and Jill Harper, uses a process called fusion polymerase chain reaction (fusion PCR) to attach a green fluorescent protein (GFP) to the gene that encodes one of the parasite’s proteins. The fused protein emits the eerie green glow that enables Carruthers to track the parasite by using an inverted light microscope (in which the lens sits below the specimen dish or flask).

The most significant development in Carruthers’ research so far relates to the role of the parasite’s secretory proteins. Carruthers’ team has been able to illustrate that Toxoplasma secretes these proteins at different stages of the invasion of the host cell. The first cohort of proteins helps the parasite bind itself to the cell; the second pushes into the cell and forms a compartment for the parasite to occupy; and the third modifies that compartment to begin taking in the cell’s resources. Carruthers and former graduate student Karen Rabenau disabled M2AP, one of the most important secretory proteins the parasite releases. “M2AP is partnered with another parasite protein called MIC2, which binds to the host cell,” Carruthers explains. He and his team found that disruption of M2AP impairs the parasite’s ability to secrete MIC2, thus proving a connection between them and invasion—and revealing a possible way to disrupt the parasite’s ability to spread.

Since cell invasion is an essential process for both Toxoplasma and its cousin Plasmodium (the malaria parasite), Carruthers notes that his research may also help malaria scientists in their quest for new drug treatments.