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 The cytoskeleton of neurons has been found to be involved in Alzheimer's disease
18.01.2019 | University of the Basque Country

nachricht Bioinspired nanoscale drug delivery method developed by WSU, PNNL researchers
10.01.2019 | Washington State University

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: Ten-year anniversary of the Neumayer Station III

The scientific and political community alike stress the importance of German Antarctic research

Joint Press Release from the BMBF and AWI

The Antarctic is a frigid continent south of the Antarctic Circle, where researchers are the only inhabitants. Despite the hostile conditions, here the Alfred...

Im Focus: Ultra ultrasound to transform new tech

World first experiments on sensor that may revolutionise everything from medical devices to unmanned vehicles

The new sensor - capable of detecting vibrations of living cells - may revolutionise everything from medical devices to unmanned vehicles.

Im Focus: Flying Optical Cats for Quantum Communication

Dead and alive at the same time? Researchers at the Max Planck Institute of Quantum Optics have implemented Erwin Schrödinger’s paradoxical gedanken experiment employing an entangled atom-light state.

In 1935 Erwin Schrödinger formulated a thought experiment designed to capture the paradoxical nature of quantum physics. The crucial element of this gedanken...

Im Focus: Nanocellulose for novel implants: Ears from the 3D-printer

Cellulose obtained from wood has amazing material properties. Empa researchers are now equipping the biodegradable material with additional functionalities to produce implants for cartilage diseases using 3D printing.

It all starts with an ear. Empa researcher Michael Hausmann removes the object shaped like a human ear from the 3D printer and explains:

Im Focus: Elucidating the Atomic Mechanism of Superlubricity

The phenomenon of so-called superlubricity is known, but so far the explanation at the atomic level has been missing: for example, how does extremely low friction occur in bearings? Researchers from the Fraunhofer Institutes IWM and IWS jointly deciphered a universal mechanism of superlubricity for certain diamond-like carbon layers in combination with organic lubricants. Based on this knowledge, it is now possible to formulate design rules for supra lubricating layer-lubricant combinations. The results are presented in an article in Nature Communications, volume 10.

One of the most important prerequisites for sustainable and environmentally friendly mobility is minimizing friction. Research and industry have been dedicated...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Our digital society in 2040

16.01.2019 | Event News

11th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Aachen, 3-4 April 2019

14.01.2019 | Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

 
Latest News

Additive manufacturing reflects fundamental metallurgical principles to create materials

18.01.2019 | Materials Sciences

How molecules teeter in a laser field

18.01.2019 | Life Sciences

The cytoskeleton of neurons has been found to be involved in Alzheimer's disease

18.01.2019 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>