Microbes that survive drug treatment often become drug-resistant. Researchers in the labs of Professors Jim Anderson and Linda Kohn of botany have determined how this happens by studying the yeast Candida albicans and its genetic changes when exposed to drugs. "Ultimately, our findings could lead to the development of companion drugs that target these sets of genes, delaying or preventing the evolution of resistance to the therapeutic drug," says doctoral student Leah Cowen, the study's lead author.
Researchers grew over 330 generations of the yeast - a common inhabitant of healthy humans that causes thrush, diaper rash and infections in women as well as life-threatening infections in immuno-compromised individuals - in the presence of the widely prescribed anti-fungal drug fluconazole. Drug resistance increased as the researchers had predicted. While they saw expected changes to the molecular pumps (which remove a variety of drugs from cells), they also noted changes in hundreds of genes. More surprisingly, they found the altered genes displayed three distinct patterns - a finding replicated in patient samples. Recognizing these patterns will make it easier for scientists to target drug therapy, Cowen says.
Funding for the research, published in Proceedings of the National Academy of Sciences, was provided by the Natural Sciences and Engineering Research Council of Canada. The drug fluconazole was supplied by Pfizer Inc.
ADDITIONAL CONTACT INFORMATION:
Leah Cowen, Department of Botany,
905-828-3995,
lcowen@credit.erin.utoronto.ca
Journal
Proceedings of the National Academy of Sciences