Nav: Home

Genome structure of malaria parasites linked to virulence

February 04, 2019

RIVERSIDE, Calif. -- An international research team led by scientists at the University of California, Riverside, and the La Jolla Institute for Immunology has found that malaria parasite genomes are shaped by parasite-specific gene families, and that this genome organization strongly correlates with the parasite's virulence.

The findings highlight the importance of spatial genome organization in gene regulation and the control of virulence in malaria parasites.

"Our results underscore the idea that compounds targeting proteins involved in establishing and maintaining the genome structure can interfere with parasite development and immune evasion," said co-lead researcher Karine Le Roch, a professor in the UC Riverside Department of Molecular, Cell and Systems Biology. "Novel intervention strategies targeting the genome structure could thus mark a breakthrough for both vaccine and drug development against malaria."

Study results appear in the Proceedings of the National Academy of Sciences.

Le Roch, co-leader Ferhat Ay, the Institute Leadership assistant professor of computational biology at La Jolla Institute for Immunology and an assistant adjunct professor at the UC San Diego School of Medicine, and colleagues investigated the 3-D genome organization in five malaria parasites and two related parasites to identify possible connections between genome architecture and pathogenicity. They found that in all five malaria parasites, genome organization is dominated by the clustering of parasite-specific gene families in 3-D space.

"Further, this 3-D genome organization in the nucleus plays a role in gene expression and pathogenicity of these deadly parasites," said Le Roch, director of the UCR Center for Infectious Disease Vector Research and a member of the UCR Institute for Integrative Genome Biology.

The most virulent species of malaria parasites use an "antigenic variation" mechanism to alter their surface proteins and avoid the host immune response. The ability of the parasite to switch its antigenic profile correlates with the parasite's high virulence. The more capable the parasite is in switching its antigenic profile, the more virulent the parasite.

The researchers found that the two most pathogenic human malaria parasites -- Plasmodium falciparum and Plasmodium knowlesi -- share unique features in the organization of gene families involved in antigenic variation. P. falciparum and P. knowlesi, they report, have evolved unique gene families -- var and SICvar, respectively -- that enable these parasites to undergo antigenic variation.

"The organization of other Plasmodium genomes is also driven by their virulence genes -- but it is not as strongly seen in them as we see in P. falciparum and P. knowlesi," Le Roch said.

When the researchers generated similar 3-D genome models for the related human parasites Babesia microti, which causes a malaria-like illness endemic in the United States, and Toxoplasma gondii, which causes toxoplasmosis in individuals with weakened immune systems, they found no association between genome structure and gene expression in general, suggesting this association is Plasmodium-specific.

"Our results, obtained by comparing the five malaria parasites with B. microti and T. gondii, strongly suggest that genome organization in malaria parasites has been shaped by parasite-specific gene families that affect virulence," Le Roch said.

The researchers also observed significant differences between malaria parasites infecting primates and rodents, suggesting the various parasite lineages have evolved different strategies to survive in their respective hosts.

"One contributing factor could be the life span of the host," Le Roch said. "Parasites infecting long-lived primates may require escape from adaptive immune responses to establish chronic infections and ensure transmission to a susceptible host, while parasites infecting short-lived rodent hosts may benefit from more flexible expression of their virulence genes."

Next, the team plans on identifying the molecular components regulating the parasite-specific genes at the chromatin structure level with the goal of identifying new targets for novel therapeutic strategies.
-end-
Le Roch and Ay were joined in the research by scientists at UC Riverside; the University of Texas Health Science Center, San Antonio; Emory University; University of Oxford; Mahidol University; Columbia University; Yale School of Medicine, New Haven; University of Nottingham; and Johns Hopkins Bloomberg School of Public Health.

Le Roch was supported in the research by grants from the National Institutes of Health and UC Riverside.

University of California - Riverside

Related Malaria Articles:

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 Umeå 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.
Free malaria tests coupled with diagnosis-dependent vouchers for over-the-counter malaria treatment
Coupling free diagnostic tests for malaria with discounts on artemisinin combination therapy (ACT) when malaria is diagnosed can improve the rational use of ACTs and boost testing rates, according to a cluster-randomized trial published this week in PLOS Medicine by Wendy Prudhomme O'Meara of Duke University, USA, and colleagues.
More Malaria News and Malaria Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Climate Mindset
In the past few months, human beings have come together to fight a global threat. This hour, TED speakers explore how our response can be the catalyst to fight another global crisis: climate change. Guests include political strategist Tom Rivett-Carnac, diplomat Christiana Figueres, climate justice activist Xiye Bastida, and writer, illustrator, and artist Oliver Jeffers.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Speedy Beet
There are few musical moments more well-worn than the first four notes of Beethoven's Fifth Symphony. But in this short, we find out that Beethoven might have made a last-ditch effort to keep his music from ever feeling familiar, to keep pushing his listeners to a kind of psychological limit. Big thanks to our Brooklyn Philharmonic musicians: Deborah Buck and Suzy Perelman on violin, Arash Amini on cello, and Ah Ling Neu on viola. And check out The First Four Notes, Matthew Guerrieri's book on Beethoven's Fifth. Support Radiolab today at Radiolab.org/donate.