A study by a multidisciplinary research team, co-directed by Worcester Polytechnic Institute (WPI), offers new insights into how virulent fungi adapt through genetic modifications to fight back against the effects of medication designed to block their spread, and how that battle leaves them temporarily weakened. These insights may provide clues to new ways to treat notoriously difficult-to-cure fungal infections like thrush and vaginitis.
The team studied patients infected with the fungus Candida albicans (C. albicans), which causes common yeast infections and more serious bloodstream infections, who were being treated with fluconazole, one of the primary antifungal drugs now in use. They found that the fungus undergoes 240 genetic changes associated with drug resistance. But those changes come with a cost, they discovered. As it battles to overcome the effects of the drug, the fungus becomes weaker, with a reduction in the traits associated with virulence. The discoveries may point toward new targets for research and the potential to develop new classes of therapeutics for hard-to-treat fungal infections.
Using next-generation DNA sequencing technology, the team looked for changes at the genetic level in 43 samples of C. albicans collected from the 11 patients over ten months. By sampling fungi from the same patients over time, researchers identified genetic mutations that correlated with the fungi’s evolving ability to overcome the effects of fluconazole in those patients. The results revealed changes in genes associated with the structure of fungi’s outer membrane and the activity of molecular pumps that can eject the drug from the yeast’s cells. Numerous other genetic mutations were found to be prevalent as drug resistance increased, though the functional impact of those changes is not known.
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