Featured Research

from universities, journals, and other organizations

Discovery aids in fight against antifungal drug resistance

Date:
February 3, 2014
Source:
University of Otago
Summary:
A research breakthrough is helping pave the way for novel antifungal drugs designed to overcome the world-wide problem of growing resistance to current treatments.

Dr. Monk, above, says the research team's breakthrough will provide new insights into mechanisms underlying fungal resistance to triazole drugs and aid in efforts to develop new broad-spectrum drugs with minimal side-effects.
Credit: University of Otago

A new University of Otago research breakthrough from the Sir John Walsh Research Institute is helping pave the way for novel antifungal drugs designed to overcome the world-wide problem of growing resistance to current treatments.

Fungal infections by organisms such Candida, Aspergillus and Cryptococcus play an increasingly significant role in disease. Infections such as thrush affect premature babies, the elderly, females of reproductive age, individuals with dry mouth and terminal cancer patients. They can be fatal; 1.4 million people die annually due to fungal infections made worse by co-infections with tuberculosis and AIDS or by medically-induced immune deficiency.

To date, efforts to expand the array of antifungal treatments available have been hindered by the lack of molecular-level understanding of potential drug targets and mechanisms causing drug resistance.

Now, Otago researchers led by Dr Brian Monk, and working with colleagues at the University of California San Francisco, have determined the complex structure of a key cell membrane protein involved in sterol metabolism and resistance in a yeast model. Their findings appear in the latest online early edition of the US journal Proceedings of the National Academy of Sciences (PNAS).

Dr Monk says the research team's feat will provide new insights into mechanisms underlying fungal resistance to triazole drugs and aid in efforts to develop new broad-spectrum drugs with minimal side-effects.

"Membrane proteins in general are important molecules in cells and they also represent around 70 per cent of all drug targets. However, they are notoriously tricky for scientists to extract from cells and successfully study, so we are delighted that we have been able to do so."

The researchers' X-ray crystallography images of the structure reveal new features likely to be held in common with up to half of all membrane proteins, including closely related proteins that modify the action of most commonly prescribed drugs.

"They tell us how the fungal enzyme and its relatives interact with the membrane and provide important clues about relationships with substrates, inhibitors and products that have broad implications for biology, drug design and personalised medicine."

Dr Monk notes that their success in solving the membrane protein structure parallels a similar recent achievement by Professor Greg Cook's team in Otago's Department of Microbiology and Immunology.

Last month, Professor Cook and colleagues published the structure of a membrane protein essential for bacteria to generate energy, a finding which opens the way to developing new classes of antimicrobial drugs. Less than 0.5% of the protein structures so far determined worldwide are for membrane proteins.

It is particularly impressive for two groups at Otago to have published such structures in 2014, which is the United Nations-sanctioned International Year of Crystallography in honour of a century of multidisciplinary contributions to humanity, Dr Monk says.

The next steps for Dr Monk and colleagues are further study of the membrane protein in several important fungal pathogens and use state-of-the-art screening technology to identify new broad-spectrum drugs that target this protein.


Story Source:

The above story is based on materials provided by University of Otago. Note: Materials may be edited for content and length.


Journal Reference:

  1. B. C. Monk, T. M. Tomasiak, M. V. Keniya, F. U. Huschmann, J. D. A. Tyndall, J. D. O'Connell, R. D. Cannon, J. G. McDonald, A. Rodriguez, J. S. Finer-Moore, R. M. Stroud. Architecture of a single membrane spanning cytochrome P450 suggests constraints that orient the catalytic domain relative to a bilayer. Proceedings of the National Academy of Sciences, 2014; DOI: 10.1073/pnas.1324245111

Cite This Page:

University of Otago. "Discovery aids in fight against antifungal drug resistance." ScienceDaily. ScienceDaily, 3 February 2014. <www.sciencedaily.com/releases/2014/02/140203155159.htm>.
University of Otago. (2014, February 3). Discovery aids in fight against antifungal drug resistance. ScienceDaily. Retrieved April 18, 2014 from www.sciencedaily.com/releases/2014/02/140203155159.htm
University of Otago. "Discovery aids in fight against antifungal drug resistance." ScienceDaily. www.sciencedaily.com/releases/2014/02/140203155159.htm (accessed April 18, 2014).

Share This



More Plants & Animals News

Friday, April 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Vermont Goat Meat Gives Refugees Taste of Home

Vermont Goat Meat Gives Refugees Taste of Home

AP (Apr. 18, 2014) Dairy farmers and ethnic groups in Vermont are both benefiting from a unique collaborative effort that's feeding a growing need for fresh and affordable goat meat. (April 18) Video provided by AP
Powered by NewsLook.com
First Ever 'Female Penis' Discovered In Animal Kingdom

First Ever 'Female Penis' Discovered In Animal Kingdom

Newsy (Apr. 18, 2014) Not only are these newly discovered bugs' sex organs reversed, but they also mate for up to 70 hours. Video provided by Newsy
Powered by NewsLook.com
The Great British Farmland Boom

The Great British Farmland Boom

Reuters - Business Video Online (Apr. 17, 2014) Britain's troubled Co-operative Group is preparing to cash in on nearly 18,000 acres of farmland in one of the biggest UK land sales in decades. As Ivor Bennett reports, the market timing couldn't be better, with farmland prices soaring over 270 percent in the last 10 years. Video provided by Reuters
Powered by NewsLook.com
Flamingo Frenzy Ahead of Zoo Construction

Flamingo Frenzy Ahead of Zoo Construction

AP (Apr. 17, 2014) With plenty of honking, flapping, and fluttering, more than three dozen Caribbean flamingos at Zoo Miami were rounded up today as the iconic exhibit was closed for renovations. (April 17) 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