Featured Research

from universities, journals, and other organizations

Drug resistance may make malaria parasites vulnerable to other substances

Date:
June 4, 2013
Source:
University of St George's London
Summary:
Malaria parasites that develop resistance to the most effective class of anti-malarial drugs may become susceptible to other treatments as a result. The discovery could reveal potential new drug options, which would be essential in the event of resistance to the best anti-malarials.

Malaria parasites that develop resistance to the most effective class of anti-malarial drugs may become susceptible to other treatments as a result. The discovery could reveal potential new drug options, which would be essential in the event of resistance to the best anti-malarials.

In a new study, researchers have shown how the anti-malarials artemisinins attack the malaria parasite by inhibiting the action of a crucial protein, and that genetic mutations in this protein can reduce the effect of the drugs. While demonstrating this, however, they also discovered that a mutation that gives the parasite resistance to artemisinins makes it more sensitive to attack by another substance, cyclopiazonic acid (CPA). CPA is thought to be too toxic to be a suitable anti-malarial treatment, but the findings suggest it could be worth pursuing derivatives of the acid as treatment options.

The study was led by researchers at St George's, University of London and has been published in The Journal of Infectious Diseases.

The artemisinin group of drugs are the most effective and widely used treatments for malaria -- used most powerfully with other drugs as artemisinin-based combination therapies -- but little is known about their mechanism of action on the malaria parasite. There are signs that the malaria parasite is developing resistance to artemisinin-based combination therapies, meaning further understanding of the drugs could be crucial to prevent them becoming obsolete.

The St George's researchers have now demonstrated that artemisinins work by acting on a protein within the parasite called a calcium pump. Calcium is essential for all living organisms as it is needed for vital cellular processes. The calcium pump regulates calcium levels in cells, and if it is not functioning properly the parasite dies.

In previous studies, the team had witnessed the same effect on the calcium pump in genetically engineered malaria parasites. However, in these studies the parasites' sensitivity to artemisinins fluctuated, so they did not give a clear indication of the drugs' mechanism of action and the findings could not be confirmed.

To provide more consistent results, the latest study used yeast cells instead of parasite cells. Yeast can be a convenient way to display and test the function of proteins from other organisms.

After confirming that artemisinins inhibited the calcium pump in the yeast model, the researchers mutated the pump to mimic three mutations previously observed to give parasites resistance to the drugs. When they did this, they saw similar resistance.

Following this, they tested whether these mutations had any effect on the action of another five substances known to have an anti-malarial effect. They found that one particular mutation that gave the pump resistance to artemisinins made it more susceptible to CPA.

Their findings also showed that the yeast model could be used to identify other drugs that harm the parasite.

Lead author Professor Sanjeev Krishna said: "CPA is a compound used in science and not in clinical practice in any way. However, it points to a proof of concept that we can look for weaknesses in the more resistant strains of the parasite. The yeast model provides a convenient and reliable method to study anti-malarials and this particular mechanism of resistance to them."

He added: "This new research supports our earlier work suggesting that the calcium pump is crucial for artemisinins' action. Understanding how this lifesaving drug works on this calcium pump and how the pump can develop drug resistance will not only allow us to better understand how to use artemisinins more effectively, but it will help us contribute to the development of new drugs to counter the potentially serious effects of artemisinin resistance."


Story Source:

The above story is based on materials provided by University of St George's London. Note: Materials may be edited for content and length.


Journal Reference:

  1. S. Pulcini, H. M. Staines, J. K. Pittman, K. Slavic, C. Doerig, J. Halbert, R. Tewari, F. Shah, M. A. Avery, R. K. Haynes, S. Krishna. Expression in Yeast Links Field Polymorphisms in PfATP6 to in Vitro Artemisinin Resistance and Identifies New Inhibitor Classes. Journal of Infectious Diseases, 2013; DOI: 10.1093/infdis/jit171

Cite This Page:

University of St George's London. "Drug resistance may make malaria parasites vulnerable to other substances." ScienceDaily. ScienceDaily, 4 June 2013. <www.sciencedaily.com/releases/2013/06/130604094530.htm>.
University of St George's London. (2013, June 4). Drug resistance may make malaria parasites vulnerable to other substances. ScienceDaily. Retrieved July 30, 2014 from www.sciencedaily.com/releases/2013/06/130604094530.htm
University of St George's London. "Drug resistance may make malaria parasites vulnerable to other substances." ScienceDaily. www.sciencedaily.com/releases/2013/06/130604094530.htm (accessed July 30, 2014).

Share This




More Plants & Animals News

Wednesday, July 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Raw: Thousands Flocking to German Crop Circle

Raw: Thousands Flocking to German Crop Circle

AP (July 30, 2014) Thousands of people are trekking to a Bavarian farmer's field to check out a mysterious set of crop circles. (July 30) Video provided by AP
Powered by NewsLook.com
Concern Grows Over Worsening Ebola Crisis

Concern Grows Over Worsening Ebola Crisis

AFP (July 30, 2014) Pan-African airline ASKY has suspended all flights to and from the capitals of Liberia and Sierra Leone amid the worsening Ebola health crisis, which has so far caused 672 deaths in Guinea, Liberia and Sierra Leone. Duration: 00:43 Video provided by AFP
Powered by NewsLook.com
At Least 20 Chikungunya Cases in New Jersey

At Least 20 Chikungunya Cases in New Jersey

AP (July 30, 2014) At least 20 New Jersey residents have tested positive for chikungunya, a mosquito-borne virus that has spread through the Caribbean. (July 30) Video provided by AP
Powered by NewsLook.com
Raw: Otters Enjoy Water Slides at Japan Zoo

Raw: Otters Enjoy Water Slides at Japan Zoo

AP (July 30, 2014) River otters were hitting the water slides to beat the summer heatwave on Wednesday at Ichikawa City's Zoological and Botanical Garden. (July 30) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins