NIH funds drug discovery for apicomplexan parasites

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Apicomplexan parasites control DNA replication differently than humans do and understanding these differences may be the key to preventing diseases such as malaria and toxoplasmosis, according to Dr. Elena Suvorova, USF researcher in the Center of Excellence in Drug Discovery and Innovation, and Department of Global Health.

She’s part of a USF College of Public Health research team who have been granted funding from the National Institutes of Health for the next five years to study the DNA licensing of apicomplexan parasites.

The team, led by Distinguished USF Health Professor Dr. Michael White of the Department of Global Health, received a total of $2.5 million. They began research in June 2016 and will continue through May 2021.

Drs. Elena Suvorova and Michael White. (Photo courtesy of USF Health Communications)

Apicomplexa parasites are a phylum of obligatory intracellular parasites causing many important diseases including malaria and toxoplasmosis.

Malaria can be a severe, potentially fatal disease, particularly when caused by Plasmodium falciparum, according to the Centers for Disease Control and Prevention, with an estimated 627,000 people dying due to infection in 2012.

Toxoplasmosis is considered to be a leading cause of death attributed to foodborne illness in the U.S., according to the CDC and is contracted from soil contaminated with cat feces, undercooked meat, and congenital transmission.

Suvorova said the overall goal of the research is to find new drugs targeting these infections.

“We’re trying to understand the general mechanisms that help parasites to divide,” Suvorova said. “We’re using the model system of Toxoplasma gondii, which is a close relative of the malaria parasite, Plasmodium spp.”

 

Image of Toxoplasma gondii parasites dividing. Provided by Ke Hu and John Murray (DOI: 10.1371/journal.ppat.0020020.g001).

“Many things that you can easily do in Toxoplasma gondii, you can’t do or it takes much longer to do in Plasmodium spp., such as genetic manipulation, large scale omics and cell biology,” she said. “We’re using Toxoplasma gondii model to understand biology of apicomplexan parasites, including malaria species so we can control and stop deadly infections. We’re looking for something essential for the parasite’s survival. In this case, it’s DNA replication.”

According to Suvorova, apicomplexan parasites evolved novel regulatory mechanisms to control DNA replication processes vital for survival. Targeting these regulators that are so different in parasites and host cells, may down the line help with finding new drugs that could potentially control deadly malaria infections.

“DNA replication is one of the key steps in the cell cycle of the living cells. In the Toxoplasma community, not many people are studying the cell cycle,” Suvorova said. “It’s discouraging, because it’s not easy. The way parasites divide is very unique and so complex that it discourages other researchers to even try.”

Suvorova and Dr. Anatoli Naumov, assistant professor, will serve as the two main researchers on the grant.

Carmelo Alvarez, research technician and lab manager, said the public health benefit of this research is highly important.

“Toxoplasma gondii still affects as many as 4,000 pregnancies in the U.S. The major public health aspect is that it belongs to the Apicomplexa, which is a group of parasites that contain within them cryptosporidium and plasmodium, which are both important human pathogens, plasmodium being the causative agent of malaria,” he said. “It’s important. It’s fulfilling work, its complex and I think it’s really important for easing human suffering around the world.”

Story by Anna Mayor, USF College of Public Health

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