Featured Research

from universities, journals, and other organizations

Molecular pathway through which common yeast becomes fungal pathogen determined

Date:
March 16, 2012
Source:
University of Toronto
Summary:
Scientists have found a molecular mechanism that plays a key role in the transition of Candida albicans yeast into disease-causing fungus -- one of the leading causes of hospital-acquired infection. The finding highlights the importance of heat in fungal growth, and provides a new target for drug therapies to counter Candida albicans infection. In an additional study, the researchers identified 224 new genetic interactors for central protein in Candida albicans.

Scientists at the University of Toronto have found a molecular mechanism that plays a key role in the transition of Candida albicans yeast into disease-causing fungus -- one of the leading causes of hospital-acquired infection. The finding highlights the importance of heat in fungal growth, and provides a new target for drug therapies to counter Candida albicans infection.

Candida albicans is a normally harmless yeast that is present in all humans. It becomes infectious in various genetic and environmental conditions, with temperature as a key determinant. It can produce infections that are mild -- persistent vaginal or gut infections, for example -- or severe, such as systemic, potentially fatal bloodstream infections in patients with AIDS or those who have undergone chemotherapy (or even a simple round of antibiotics).

The molecular workings of Candida albicans were mapped for the first time in 2009 by Professor Leah Cowen of the University of Toronto's Department of Molecular Genetics, whose lab showed that growth of the fungus is tied to the function of a "molecular chaperone" called heat- shock protein 90 (Hsp90). In a study that will appear in the March 20 edition of the journal Current Biology, Prof. Cowen and her colleagues detail a mechanism that controls response to elevated temperature through a protein named Hms1 in conjunction with a cyclin (another type of protein) and its partner protein called a cyclin-dependent kinase.

"This circuitry fundamentally influences how Candida albicans senses temperature, which is crucial for Candida's ability to cause disease," said Prof. Cowen, who holds the Canada Research Chair in Microbial Genomics and Infectious Disease -- a prestigious five-year award for which she was renewed this week.

"We were looking for a transcription factor at the end of a pathway we previously showed was key to the change in shape of the fungus that accompanies elevated temperature or compromise of Hsp90 function, and instead we found an entirely new pathway, with components that haven't been characterized in Candida, so it was very surprising," said Prof. Cowen.

The researchers also showed that deletion of Hms1 inhibits Candida albicans infection, pointing toward a possible clinical therapy. "We observed those weaker disease phenotypes in an insect model system, but the results suggest it may also work in more complicated systems," said Prof. Cowen.

The source of pesky vaginal and gut infections, Candida albicans is a burgeoning problem on implanted medical devices -- it's fatal in roughly one-third of device-associated infections -- and is the fourth-leading cause of hospital-acquired infection. The number of acquired fungal bloodstream infections has increased by more than 200% over the last twenty years, owing in part to growing numbers of AIDS and cancer survivors whose treatments have compromised their immune function.

On finding that the Hms1 pathway affects the growth and development of Candida albicans, and knowing of other key regulators through which Hsp90 operates and suspecting many more exist, Prof. Cowen and her lab examined other pathways and proteins that interact with Hsp90 in another study.

In collaboration with Professor Gary Bader at U of T's Donnelly Centre for Cellular and Biomolecular Research, Prof. Cowen's group mapped a much larger portion of the chaperone network with which Hsp90 interacts through a "chemical genomics" approach that had never been applied to Candida albicans. "If we want to have a more global understanding of what Hsp90 is doing during the transition of this fungus between distinct morphological states with different disease causing properties, we need to take global approaches to determine what its interacting with," said Prof. Cowen.

Their results, published online today in the journal PLoS Genetics, showed 226 genetic interactors with Hsp90 in various conditions, such as different temperatures and during exposure to anti-fungal drugs. Of those interactions, 224 were previously unknown. "That's a lot," said Prof. Cowen. "We now have a myriad of new targets through which Hsp90 could be regulating morphogenesis and drug resistance in Candida."

As well, the researchers drew several predictive rules from their study that govern the Hsp90 chaperone network. Some interactors were only important in a small subset of stress conditions, and these are likely to function "downstream" of Hsp90 regulating specialized cellular processes. Other interactors were important in many stress conditions, and so are likely to work "upstream" of Hsp90 regulating its function.

"Hsp90 stabilizes many proteins, but previously nobody could predict what made an Hsp90 client. That we can make such predictions from the chaperone network is pretty cool and unanticipated, so we're further ahead than we expected," said Prof. Cowen.


Story Source:

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


Journal Reference:

  1. RebeccaS. Shapiro, Adnane Sellam, Faiza Tebbji, Malcolm Whiteway, Andre Nantel, LeahE. Cowen. Pho85, Pcl1, and Hms1 Signaling Governs Candida albicans Morphogenesis Induced by High Temperature or Hsp90 Compromise. Current Biology, 2012; DOI: 10.1016/j.cub.2012.01.062

Cite This Page:

University of Toronto. "Molecular pathway through which common yeast becomes fungal pathogen determined." ScienceDaily. ScienceDaily, 16 March 2012. <www.sciencedaily.com/releases/2012/03/120316112642.htm>.
University of Toronto. (2012, March 16). Molecular pathway through which common yeast becomes fungal pathogen determined. ScienceDaily. Retrieved July 28, 2014 from www.sciencedaily.com/releases/2012/03/120316112642.htm
University of Toronto. "Molecular pathway through which common yeast becomes fungal pathogen determined." ScienceDaily. www.sciencedaily.com/releases/2012/03/120316112642.htm (accessed July 28, 2014).

Share This




More Health & Medicine News

Monday, July 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
Powered by NewsLook.com
West Africa Gripped by Deadly Ebola Outbreak

West Africa Gripped by Deadly Ebola Outbreak

AFP (July 28, 2014) The worst-ever outbreak of the deadly Ebola epidemic grips west Africa, killing hundreds. Duration: 00:48 Video provided by AFP
Powered by NewsLook.com
Trees Could Save More Than 850 Lives Each Year

Trees Could Save More Than 850 Lives Each Year

Newsy (July 27, 2014) A national study conducted by the USDA Forest Service found that trees collectively save more than 850 lives on an annual basis. Video provided by Newsy
Powered by NewsLook.com
Google's Next Frontier: The Human Body

Google's Next Frontier: The Human Body

Newsy (July 27, 2014) Google is collecting genetic and molecular information to paint a picture of the perfectly healthy human. Video provided by Newsy
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