KETR

A Remnant From Algae In Malaria Parasite May Prove Its Weakness

Aug 30, 2011
Originally published on August 31, 2011 11:54 am

Scientists may have found a critical weakness in Plasmodium falciparum, the parasite that causes malaria. Researchers say the discovery provides a promising target for new malaria therapies.

The weakness is related to a structure inside malaria cells called an apicoplast. About a decade ago, molecular biologist Joseph DeRisi of the University of California, San Francisco became interested in an organelle inside the malaria parasites' cells known as an apicoplast. No one was completely sure what the apicoplast did.

Enter Ellen Yeh. She's a recent graduate of Stanford with an M.D. and a Ph.D. who came to work in DeRisi's lab.

Yeh is interested in metabolic pathways. These are the biochemical steps things like apicoplasts use to make the chemicals they make. Actually, Yeh is more than just interested in metabolic pathways. "I love metabolic pathways," she says.

Yeh started looking at the metabolic pathways in the parasite's apicoplasts. "There actually only seemed to be one pathway that the parasite really really needed. And that everything else it probably could find other ways of getting those products."

To prove it, she created a colony of parasites that were missing their apicoplasts. Normally, without an apicoplast, the parasites would just die. But Yeh added back the chemical from the important metabolic pathway to the tubes the parasites were growing in. "It was a pretty amazing day in the lab when I walked in and those parasites were still alive with no apicoplasts, but because I had added that one chemical they were still living," she says. The work appears in the journal Plos Biology.

Yeh's colleague DeRisi says knowing this is a critical chemical for the parasite is a game-changer. "Now we can design, or look for specific kinds of drugs that inhibit just this one thing instead of just shooting in the dark hoping that you find a drug that disrupts something that you hope might be essential," he says.

In fact, DeRisi already has a good place to start: fosmidomycin, a new drug that targets the apicoplast. But Boris Striepen, a malaria researcher at the University of Georgia, says fosmidomycin is not a great drug, because it's excreted from the human body too fast. He says the new findings should make the search for better drugs much easier.

Even so, Striepen says the malaria parasite isn't going to go down without a fight. "There is not one discovery that can be made and then that problem goes away and can be put to rest. I think it needs effort of new drugs to stay abreast."

Now, apicoplasts are odd. They don't show up in most species, and we don't have them in our cells. They have their own DNA, separate from the parasite's main DNA.

When scientists analyzed the apicoplasts DNA, they were astonished to find that it was most closely related to the DNA in algae. "It's actually thought that the malaria parasite incorporated an algal cell early on, and that the thing we call the apicoplast is the remnant of the algal cell," says Sean Prigge at the Johns Hopkins Malaria Institute .

So a remnant of algae may help bring down one of the world's most deadly parasites.

Copyright 2018 NPR. To see more, visit http://www.npr.org/.

DAVID GREENE, host:

Scientists may have found a new way to attack malaria. It's a disease that kills some two million people each year. The malaria parasite has become resistant to many drugs. But now two scientists have discovered a weakness in one of the world's most deadly parasites. It's a chemical the parasite needs to survive. The discovery points the way to new therapies.

NPR's Joe Palca explains.

JOE PALCA: This story begins inside a parasite's lone cell. There's a structure inside the cell called an apicoplast. It was clearly making chemicals the parasite needed to survive, but no one was quite sure what. Joseph DeRisi got interested in this tiny structure about a decade ago. DeRisi is at the University of California San Francisco. At first, DeRisi made some progress exploring the new structure.

Dr. JOSEPH DERISI (University of California San Francisco): But the work sort of stagnated after that, and it wasn't until Ellen came along with some new ideas that the work on the apicoplast picked back up.

PALCA: Ellen is Ellen Yeh, a recent graduate of Stanford with an MD and a PhD who came to work in DeRisi's lab. Yeh is interested in metabolic pathways. These are the biochemical steps things like apicoplasts use to make the chemicals they make. Actually, Yeh is more than just interested in metabolic pathways.

Dr. ELLEN YEH (University of California San Francisco): I love metabolic pathways.

PALCA: Yeh started looking at the metabolic pathways in the parasite's apicoplasts.

Dr. YEH: There would actually seem to be only one pathway that the parasite really, really needed.

PALCA: Everything else could be made somewhere else in the cell. To prove this one pathway made a vital chemical, she created a colony of parasites that were missing their apicoplasts. Normally, if this structure is missing, the parasites would just die. But Yeh added back the missing chemical.

Dr. YEH: It was a pretty amazing day in the lab when I walked in and those parasites were still alive with no apicoplasts, but because I had added that one chemical, they were still living.

PALCA: Yeh's colleague Joe DeRisi says knowing this is a critical chemical for the parasite is a game changer.

Dr. DERISI: Because now we can design or look for specific kinds of drugs that inhibit just this one thing, instead of just shooting in the dark, hoping that you find a drug that disrupts something that you hope might be essential.

PALCA: Other scientists who've seen the new research - which appears in the journal PLoS Biology, in case you're interested - other scientists are impressed. Boris Striepen also studies apicoplasts. He's at the University of Georgia. But as impressed as he is, Striepen says the malaria parasite isn't going to go down without a fight.

Dr. BORIS STRIEPEN (University of Georgia): There's not one discovery that can be made, and then that problem goes away and can be put to rest. I think it needs a constant effort of new drugs to stay abreast.

PALCA: Now, I have to tell you one other interesting thing about apicoplasts. They're an odd structure. They don't occur in most cells. We don't have them, for example. And they have their own DNA, separate from the parasite's main DNA.

Sean Prigge is at the Johns Hopkins Malaria Institute. He says when scientists analyzed the apicoplasts' DNA, they were astonished to find that it was most closely related to the DNA in algae.

Dr. SEAN PRIGGE (John Hopkins Malaria Institute): It's actually thought that the malaria parasite incorporated an algal cell early on, and that the thing we call the apicoplast is the remnants of the algal cell.

PALCA: That's typical of evolution. A species takes what works and keeps it. So a remnant of algae may help bring down one of the world's most deadly parasites.

Joe Palca, NPR News, Washington. Transcript provided by NPR, Copyright NPR.