Scientists discover chemical modification in human malaria parasite DNA

December 11, 2013

RIVERSIDE, Calif. -- Say "malaria" and most people think "mosquito," but the buzzing, biting insect is merely the messenger, delivering the Plasmodium parasites that sickened more than 200 million people globally in 2010 and killed about 660,000. Worse, the parasite is showing resistance to artemisinin, the most effective drug for treating infected people.

Now University of California, Riverside researchers who are trying to understand the biology of the parasite have discovered a potential weakness--low levels of DNA methylation in Plasmodium's genome "that may be critical to the survival of the parasite," said Karine Le Roch, an associate professor of cell biology, who led the research.

DNA methylation is a biochemical process involving the modification of DNA that plays an important role in development and disease.

A paper about the findings of Le Roch and her team, titled "Genome-wide Mapping of the DNA Methylation in the Human Malaria Parasite," appears in the December issue of the journal Cell Host & Microbe.

DNA methylation is a big deal in humans; it is so essential for normal development that abnormal DNA methylation patterns have been linked with many diseases, including cancers and neurological disorders, such as Alzheimer's disease. Until now, the existence of DNA methylation in the Plasmodium parasite was disputable, Le Roch said. There were published contradicting studies that used old technology to search for methylation, but Le Roch's team was able to confirm low levels of methylation using classical molecular approaches as well as new sequencing technology.

The DNA methylation enzyme found in Plasmodium is also quite different than the one in humans, Le Roch said, "and because it is different we can eventually find a way to target it and shut it down. If a drug can be developed that specifically inhibits the methylation enzyme, it could kill the parasite in infected humans."

Researchers are keen to find a new drug against malaria, since mutations in the parasite have made it resistant to the most effective drugs on the market. "We need a new drug every five years," Le Roch said, "because the parasites always find a way to develop resistance against a drug."

Le Roch's ultimate goal is to map the regulatory networks controlling the entire life cycle of the Plasmodium parasite. She reasons that researchers really need to understand the entire biology of the parasite and how it replicates. "We're trying to find its Achilles heel," she said. "If you look at only one level, it's not going to give you the answer. We need to put all the pieces of the puzzle together."

Plasmodium's life cycle is very complex as it lives in both humans and mosquitoes. The parasite moves to the salivary glands of an infected mosquito. Once the mosquito bites a human, the parasite is injected into the blood stream and quickly reaches the liver cells, where it rapidly reproduces asexually, creating thousands of new parasites that move into red blood cells, their favorite food source. The parasite is transmitted from humans to mosquitoes when a mosquito draws blood from an infected human.
-end-
Le Roch was joined in the study by UCR's Nadia Ponts, Lijuan Fu, Elena Y. Harris, Jing Zhang, Duk-Won D. Chung, Michael Cervantes, Jacques Prudhomme, Evelien M. Bunnik, Elisandra M. Rodrigues, Stefano Lonardi, Glenn R. Hicks and Yinsheng Wang; and Vessela Atanasova-Penichon and Enric Zehraoui at the French National Institute for Agricultural Research (INRA), France.

The research was funded by a grant from the National Institutes of Health to Le Roch and a grant from the National Science Foundation to Lonardi.

Le Roch and colleagues published two other papers about their findings in November--"Polysome profiling reveals translational control of gene expression in the human malaria parasite Plasmodium falciparum" in the journal Genome Biology and "The multifunctional autophagy pathway in the human malaria parasite, Plasmodium falciparum," in the journal Autophagy.

The University of California, Riverside (http://www.ucr.edu) is a doctoral research university, a living laboratory for groundbreaking exploration of issues critical to Inland Southern California, the state and communities around the world. Reflecting California's diverse culture, UCR's enrollment has exceeded 21,000 students. The campus opened a medical school in 2013 and has reached the heart of the Coachella Valley by way of the UCR Palm Desert Center. The campus has an annual statewide economic impact of more than $1 billion. A broadcast studio with fiber cable to the AT&T Hollywood hub is available for live or taped interviews. UCR also has ISDN for radio interviews. To learn more, call (951) UCR-NEWS.

University of California - Riverside

Related Malaria Articles from Brightsurf:

Clocking in with malaria parasites
Discovery of a malaria parasite's internal clock could lead to new treatment strategies.

Breakthrough in malaria research
An international scientific consortium led by the cell biologists Volker Heussler from the University of Bern and Oliver Billker from the UmeƄ University in Sweden has for the first time systematically investigated the genome of the malaria parasite Plasmodium throughout its life cycle in a large-scale experiment.

Scientists close in on malaria vaccine
Scientists have taken another big step forward towards developing a vaccine that's effective against the most severe forms of malaria.

New tool in fight against malaria
Modifying a class of molecules originally developed to treat the skin disease psoriasis could lead to a new malaria drug that is effective against malaria parasites resistant to currently available drugs.

Malaria expert warns of need for malaria drug to treat severe cases in US
The US each year sees more than 1,500 cases of malaria, and currently there is limited access to an intravenously administered (IV) drug needed for the more serious cases.

Monkey malaria breakthrough offers cure for relapsing malaria
A breakthrough in monkey malaria research by two University of Otago scientists could help scientists diagnose and treat a relapsing form of human malaria.

Getting to zero malaria cases in zanzibar
New research led by the Johns Hopkins Center for Communication Programs, Ifakara Health Institute and the Zanzibar Malaria Elimination Program suggests that a better understanding of human behavior at night -- when malaria mosquitoes are biting -- could be key to preventing lingering cases.

Widely used malaria treatment to prevent malaria in pregnant women
A global team of researchers, led by a research team at the Liverpool School of Tropical Medicine (LSTM), are calling for a review of drug-based strategies used to prevent malaria infections in pregnant women, in areas where there is widespread resistance to existing antimalarial medicines.

Protection against Malaria: A matter of balance
A balanced production of pro and anti-inflammatory cytokines at two years of age protects against clinical malaria in early childhood, according to a study led by ISGlobal, an institution supported by ''la Caixa'' Foundation.

The math of malaria
A new mathematical model for malaria shows how competition between parasite strains within a human host reduces the odds of drug resistance developing in a high-transmission setting.

Read More: Malaria News and Malaria Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.