Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Master of antimalarial resistance

24.09.2004


A malaria parasite gene called pfcrt, already confirmed as the culprit behind resistance to the drug chloroquine in the malaria species Plasmodium falciparum, may be responsible for resistance to several other antimalarial drugs as well, a team of researchers reports in the 24 September issue of the journal Molecular Cell.



The discovery of pfcrt’s "central role" in malarial drug resistance could "help in the development of new therapeutic strategies that are effective against chloroquine-resistant parasites," said David Fidock of Albert Einstein College of Medicine, one of the lead authors of the paper.

Nearly three million people, mostly children, die from malaria each year. Chloroquine is one of the most affordable and widely used antimalarial drugs available, but chloroquine-resistant malaria has become an increasingly serious problem in the developing world, with death rates rising as a consequence.


The experiments conducted by Fidock and colleagues suggest that previously unknown mutations in the pfrct gene are associated with Plasmodium falciparum’s resistance to halofantrine and amantadine. The two drugs are used to treat mild to moderate cases of chloroquine-resistant malaria. Fidock said pfcrt’s role in halofantrine and amantadine resistance was "a big surprise actually, for both drugs. We thought initially that pfcrt was only critical for chloroquine."

The researchers uncovered the new pfcrt mutations after gradually creating strains of malaria resistant to halofantrine and amantadine treatment. As resistance to these two drugs increased, however, the parasites lost their resistance to chloroquine. This unusual pattern--gaining resistance to one drug while simultaneously losing resistance to another--may shed light on the exact role that pfcrt plays in resistance, according to Fidock and colleagues.

When a human is infected with malaria, the parasite lodges itself inside the red blood cells of its new host, drawing on the cells’ hemoglobin molecules for sustenance. As the parasite digests the hemoglobin inside a membrane pocket called the digestive vacuole, it creates a toxic byproduct called free heme. Normally, the parasite detoxifies the free heme by turning it into a product called hemozoin. As an antimalarial drug, chloroquine works by blocking this detoxification process.

The protein produced by the pfcrt gene is located in this digestive vacuole and may act as its gatekeeper. In chloroquine-resistant malaria, mutations in pfcrt may encourage chloroquine to "leak" out of the vacuole before it has a chance to stop the heme detoxification process. The pfcrt mutations seen in halofantrine and amantadine resistance seem to slow down this leak, restoring the parasite’s sensitivity to chloroquine therapy, the researchers suggest.

Fidock and colleagues note that one of the newly discovered pfcrt mutations can be found in a strain of malaria from Southeast Asia, suggesting their lab data have a parallel in the real world. The other members of the research team include Stephen Ward, Mathirut Mungthin and Patrick Bray of the Liverpool School of Tropical Medicine and Viswanathan Lakshmanan, David Johnson, and Amar Bir Singh Sidhu of Albert Einstein College of Medicine. The study was supported in part by the Wellcome Trust UK and BBSRC, the National Institutes of Health and the Ellison Medical Foundation.

David J. Johnson, David A. Fidock, Mathirut Mungthin, Viswanathan Lakshmanan, Amar Bir Singh Sidhu, Patrick G. Bray, and Stephen A. Ward: "Evidence for a Central Role for PfCRT in Conferring Plasmodium falciparum Resistance to Diverse Antimalarial Agents"

Heidi Hardman | EurekAlert!
Further information:
http://www.cell.com

More articles from Health and Medicine:

nachricht GLUT5 fluorescent probe fingerprints cancer cells
20.04.2018 | Michigan Technological University

nachricht Scientists re-create brain neurons to study obesity and personalize treatment
20.04.2018 | Cedars-Sinai Medical Center

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Tiny microenvironments in the ocean hold clues to global nitrogen cycle

23.04.2018 | Earth Sciences

Joining metals without welding

23.04.2018 | Trade Fair News

Researchers illuminate the path to a new era of microelectronics

23.04.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>