Nat Rev Microbiol. 2008 Mar;6(3):187-98.

The evolution of fungal drug resistance: modulating the trajectory from genotype to phenotype.

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Department of Molecular Genetics, University of Toronto, Medical Sciences Building, Room 4368, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada. leah.cowen@utoronto.ca

Abstract

The emergence of drug resistance in pathogenic microorganisms provides an excellent example of microbial evolution that has had profound consequences for human health. The widespread use of antimicrobial agents in medicine and agriculture exerts strong selection for the evolution of drug resistance. Selection acts on the phenotypic consequences of resistance mutations, which are influenced by the genetic variation in particular genomes. Recent studies have revealed a mechanism by which the molecular chaperone heat shock protein 90 (Hsp90) can alter the relationship between genotype and phenotype in an environmentally contingent manner, thereby 'sculpting' the course of evolution. Harnessing Hsp90 holds great promise for treating life-threatening infectious diseases.

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