Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Gene expands malaria’s invasion options


The malaria parasite Plasmodium falciparum uses different pathways to invade red blood cells, evading the body’s immune system and complicating efforts to create effective vaccines against the disease. A research team led by Australia’s Alan F. Cowman, an international research scholar with the Howard Hughes Medical Institute, has identified a gene that the parasite uses to switch back and forth between invasion pathways.

Researchers from the Scripps Research Institute in La Jolla, California, and the Genomics Institute of the Novartis Research Foundation in San Diego contributed to the work, which was published in the August 26, 2005, issue of Science.

P. falciparum causes the most lethal form of malaria, which results in one million deaths a year worldwide.

Some P. falciparum strains invade red blood cells via protein receptors on the surface that contain a sugar known as sialic acid. If scientists treat blood cells with an enzyme to remove sialic acid, the parasite can no longer invade. Other strains – including one called W2mef – can invade using the sialic acid receptors, but also have the ability to switch to other pathways if necessary.

"It’s a bit like someone trying to get into a house with different doors," says. Cowman of The Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, and the study’s senior author. "When you remove sialic acid, you block half the doors. W2mef normally goes in through the receptors with sialic acid, but it can switch – so it has two methods of entry."

To investigate how the parasite manages to switch to an alternative mode of blood cell invasion, Cowman and colleagues produced lines of the W2mef parasite that used sialic acid for invasion, and lines that could invade without it. Then they compared the differences in gene activity between the two types and identified two genes that warranted further study.

The team found only two genes whose activity differed between parasites that used sialic acid and those that did not. The first of these was a gene known as P. falciparum reticulocyte-binding like homolog 4 (PfRh4) that’s similar to other genes known to play a role in the invasion of red blood cells by P. falciparum and related parasites. The second gene, EBA165, did not appear to produce a functional protein, and the scientists suspect it had been activated only because it was physically adjacent to PfRh4. Using a second, more quantitative approach, the team found that the two genes were 60- to-80 times more active in the sialic acid-independent parasites than in those that needed the sugar for cell entry.

These results suggested that activation of the PfRh4 gene was required for the parasite to make the switch to sialic acid-independent invasion. Indeed, the team was able to find PfRh4 protein in sialic acid-independent parasites, but not in the sialic acid-dependent lines. And when the group constructed parasites in which the PfRh4 gene was disrupted, they found that those parasites would not grow in the absence of sialic acid, although they grew normally on cells with the sugar – further suggesting that activation of the PfRh4 gene is required for switching from sialic acid-dependent to –independent invasion.

"Activation of PfRh4 represents a previously unknown mechanism to switch invasion pathways and provides P. falciparum with exquisite adaptability in the face of receptor changes and immune system responses," the team concluded.

The results have important implications for the design of anti-malaria vaccines. The molecule on the parasite that binds to sialic acid receptors on host cells is considered a target in anti-malaria medications, but Cowman notes that if only that gene is blocked, some parasites can still use PfRh4 to switch to other means of entry. "If both genes are disrupted, it blocks both ways of getting in," he says.

Cindy Fox Aisen | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Don't Give the Slightest Chance to Toxic Elements in Medicinal Products
23.03.2018 | Physikalisch-Technische Bundesanstalt (PTB)

nachricht North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Space observation with radar to secure Germany's space infrastructure

Satellites in near-Earth orbit are at risk due to the steady increase in space debris. But their mission in the areas of telecommunications, navigation or weather forecasts is essential for society. Fraunhofer FHR therefore develops radar-based systems which allow the detection, tracking and cataloging of even the smallest particles of debris. Satellite operators who have access to our data are in a better position to plan evasive maneuvers and prevent destructive collisions. From April, 25-29 2018, Fraunhofer FHR and its partners will exhibit the complementary radar systems TIRA and GESTRA as well as the latest radar techniques for space observation across three stands at the ILA Berlin.

The "traffic situation" in space is very tense: the Earth is currently being orbited not only by countless satellites but also by a large volume of space...

Im Focus: Researchers Discover New Anti-Cancer Protein

An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.

The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...

Im Focus: Researchers at Fraunhofer monitor re-entry of Chinese space station Tiangong-1

In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.

Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...

Im Focus: Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.

They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

New solar solutions for sustainable buildings and cities

23.03.2018 | Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

Latest News

For graphite pellets, just add elbow grease

23.03.2018 | Materials Sciences

Unique communication strategy discovered in stem cell pathway controlling plant growth

23.03.2018 | Agricultural and Forestry Science

Sharpening the X-ray view of the nanocosm

23.03.2018 | Physics and Astronomy

Science & Research
Overview of more VideoLinks >>>