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Genomic analysis leads to better anti-fungal

by Tim Lougheed May 4 / 15
Image above: The fungus Alternaria solani conidia produces a disease in tomatoes and potatoes called early blight. Image courtesy of Eric McKenzie, PaDIL

CIFAR researchers used a sophisticated genomic analysis technique to discover a naturally-occurring chemical that could be used to fight harmful fungi. The same technique could lead to other fungicides and antibiotics to fight microbes that have developed resistance to conventional drugs.

Senior Fellow Charles Boone (University of Toronto) and Fellow Chad Myers (University of Minnesota) are in the Genetic Networks program and are co-authors on the paper. The chemical they discovered is called poacic acid, and is one of a family of organic compounds found in the cell walls of most plants.

The discovery demonstrates the potential of a novel chemical genomics platform that they developed in collaboration with an international network of institutions and investigators. This system maps the genetic interactions between five million gene pairs in the yeast Saccharomyces cerevisiae, and can be used to reveal how an unknown substance affects a cell.

The result was hailed by Science in 2010 as the definitive outline of a cell’s “genetic landscape”, which could then be interrogated with bioactive compounds. Boone contrasts this strategy with the heavy-lifting that most pharmaceutical firms undertake in their search for new drugs.

“The advantage of our system is that it’s a whole-cell assay,” he explains. “It’s not like the traditional drug screening system, which takes an enzymatic reaction and runs 100,000 compounds past it to find which ones can inhibit it. We take all the compounds that are bioactive and then we figure out what targets they go after.”

The work on poacic acid took advantage of an extensive database of such compounds at the RIKEN Center for Sustainable Resource Science in Japan, where Boone is cross-appointed. One of his post-doctoral students, Jeff Piotrowski, used the chemical genomics platform to turn this database into a means of conducting high-throughput screening. He now works for the Great Lakes Bioenergy Research Center at the University of Wisconsin–Madison.

Piotrowski came up with the name for poacic acid, which could open up a valuable niche in the arsenal of agricultural fungicides. Most of these products are based on copper sulphate, which can accumulate in soil to toxic concentrations. The addition of an entirely new input should likewise prevent fungi from becoming resistant to such pesticides.

Above all, this finding points to an innovative path in the search for other new antifungal or antibacterial agents.

“We still have to develop further methods to get to the target efficiently,” concludes Boone. “But the ultimate goal is to be able to go from a bioactive compound to its target very quickly.”