Lab Canada

Researchers discover protein powering drug resistance in fungal infections

Toronto, ON – Researchers at the University of Toronto have identified for the first time a protein which enables a deadly form of fungal infection to become drug resistant, opening up new treatment opportunities.

In research published on August 26 in the journal PLoS Pathogens, Professor Leah Cowen of the University of Toronto’s Department of Molecular Genetics and her team collaborated with colleagues from Duke University in identifying protein kinase C (or PKC) as a key means by which dangerous fungal infections become resistant to antifungal drugs.

“Given the spread of drug resistance and the growing number of people with a compromised immune system, impairing PKC’s role in rendering fungal pathogens drug-resistant will be important for reducing the threat posed by human fungal infections,” Dr Cowen said.

Dr Cowen and her colleagues used a yeast model to screen 1,280 pharmacologically active compounds – drugs used in the treatment of diverse human conditions – and found that three out of seven drugs which abolished resistance in the leading human fungal pathogen, Candida albicans (or C. albicans) had one thing in common; the drugs inhibited PKC, which controls the strength of the cell wall when it responds to stress.

“Impairing PKC, either through potent drugs or genetic techniques, opens up a new strategy for fighting fungal infections like those caused by C. albicans,” said Dr Cowen, Canada Research Chair in Microbial Genomics & Infectious Disease.

The work follows on research published in July 2009 by Dr Cowen and colleagues which identified the role of the molecular chaperone known as heat shock protein 90 (Hsp90) in making C. albicans drug resistant. In a March 2009 paper published in the journal Current Biology, she reported that Hsp90 acted as a kind of thermostat for C. albicans; shutting down this temperature-sensor can shut down the spread of infection.

Candida albicans can cause a wide range of disease from superficial infections such as yeast infections to life-threatening infections in the bloodstream. It can be especially lethal for people with compromised immune systems, such as those with AIDS or undergoing treatment for cancer or organ transplantation. C. albicans is the most frequently encountered Candida species in the clinic and is the fourth most common cause of hospital acquired infectious disease with mortality rates approaching 50%.