Featured Research

from universities, journals, and other organizations

Molecular Models Advance The Fight Against Malaria

Date:
April 28, 2005
Source:
Dartmouth Medical School
Summary:
Research from Dartmouth Medical School, demonstrating how malaria parasites form mutations that make them stubbornly resistant to drug therapy, may hold the key to a new treatments for a disease that afflicts more than half a billion people worldwide.

A mosquito, the vector of the malaria parasite, is surrounded by four molecular models that show how the antimalarial drug atovaquone loses potency against emerging resistant strains as binding of atovaquone (green) is modified by mutations in cytochrome b.
Credit: Image courtesy of Dartmouth Medical School

HANOVER, NH -- Research from Dartmouth Medical School, demonstrating how malaria parasites form mutations that make them stubbornly resistant to drug therapy, may hold the key to a new treatments for a disease that afflicts more than half a billion people worldwide.

The scientists developed disease models using yeast and successfully introduced five mutations that make malaria resistant to the anti-malarial drug, atovaquone. The study, featured as the cover story of the April 29 Journal of Biological Chemistry, paves the way for using these models to test new drugs that could suppress malaria's ability to mutate against current therapy. "This is the first quantitative explanation for malaria's drug resistance," said Dr. Bernard Trumpower, professor of biochemistry at Dartmouth Medical School and head of the study. "In addition to confirming the belief that the resistance was due to these mutations, we have created a practical research tool to design new, improved versions of the drug using these resistant strains."

Malaria, transmitted by Plasmodium falciparum, a parasite carried by mosquitoes, has developed resistance to almost every anti-malarial drug introduced in the past 30 years. Although atovaquone is one of the most recent drugs on the market, there is significant evidence that malaria parasites are quickly developing resistance to that drug as well. According to WHO estimates, 40% of the world's population are currently at risk of the disease and approximately 2 million people, mostly children, are killed by malaria annually worldwide. Today marks Africa Malaria Day, organized to promote awareness of the disease in a country where a child is killed every 30 seconds by malaria.

Investigating ways to counter the mutations and sustain the efficacy of anti-malarial drugs, Trumpower and his colleagues continued their work on previous studies using yeast enzymes to explore atovaquone resistance. It is not possible to grow enough malaria parasites to isolate and study the respiratory enzyme cytochrome bc1 complex, which the parasites need to live and multiply. A protein subunit of the bc1 complex is where the malaria parasite mutates to counter anti-malarial drug therapies. Yeast is an effective resource because it can be safely grown in large quantities and can be easily modified to take on the qualities of more dangerous pathogens, without risking human infection.

When the researchers genetically transferred mutations into the yeast surrogates, the yeast acquired resistance to atovaquone just as the malaria parasites had done. The team was then able to apply computerized modeling techniques to illustrate exactly how the drug interacted with the cytochrome bc1 complex -- the respiratory enzyme the parasites need to live and multiply -- on a molecular level. With this new understanding of how the parasites were able to counter the effects of atovaquone, researchers can now design new anti-malarial drugs with features making the appearance of resistance more unlikely.

"Within the next 3-5 years, we hope to develop a new drug that will finally empower us to treat this terrible disease," said Trumpower.

Dartmouth Medical School co-authors of the paper are Dr. Jacques Kessl, research associate in biochemistry, Kevin Ha, Anne Merritt and Benjamin Lange. Other co-authors are Dr. Brigitte Meunier and Philip Hill from the Wolfson Institute for Biomedical Research in London and Dr. Steven Meshnick from the University of North Carolina, Chapel Hill.


Story Source:

The above story is based on materials provided by Dartmouth Medical School. Note: Materials may be edited for content and length.


Cite This Page:

Dartmouth Medical School. "Molecular Models Advance The Fight Against Malaria." ScienceDaily. ScienceDaily, 28 April 2005. <www.sciencedaily.com/releases/2005/04/050425201436.htm>.
Dartmouth Medical School. (2005, April 28). Molecular Models Advance The Fight Against Malaria. ScienceDaily. Retrieved October 23, 2014 from www.sciencedaily.com/releases/2005/04/050425201436.htm
Dartmouth Medical School. "Molecular Models Advance The Fight Against Malaria." ScienceDaily. www.sciencedaily.com/releases/2005/04/050425201436.htm (accessed October 23, 2014).

Share This



More Health & Medicine News

Thursday, October 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Working Mother (Oct. 22, 2014) Is your child ready? Video provided by Working Mother
Powered by NewsLook.com
U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

Newsy (Oct. 22, 2014) Now that the U.S. is restricting travel from West Africa, some are dropping questions about a travel ban and instead asking about visa bans. Video provided by Newsy
Powered by NewsLook.com
US to Track Everyone Coming from Ebola Nations

US to Track Everyone Coming from Ebola Nations

AP (Oct. 22, 2014) Stepping up their vigilance against Ebola, federal authorities said Wednesday that everyone traveling into the US from Ebola-stricken nations will be monitored for symptoms for 21 days. (Oct. 22) Video provided by AP
Powered by NewsLook.com
Doctors Help Paralysed Man Walk Again, Patient in Disbelief

Doctors Help Paralysed Man Walk Again, Patient in Disbelief

AFP (Oct. 22, 2014) Polish doctors describe how they helped a paralysed man walk again, with the patient in disbelief at the return of sensation to his legs. Duration: 1:04 Video provided by AFP
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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