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 Chronic stress induces fatal organ dysfunctions via a new neural circuit
21.08.2017 | Hokkaido University

nachricht New malaria analysis method reveals disease severity in minutes
14.08.2017 | University of British Columbia

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: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Nagoya physicists resolve long-standing mystery of structure-less transition

21.08.2017 | Materials Sciences

Chronic stress induces fatal organ dysfunctions via a new neural circuit

21.08.2017 | Health and Medicine

Scientists from the MSU studied new liquid-crystalline photochrom

21.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>