When Candida albicans encounters stressful conditions, does it curl up and die? No! According to a paper just published in mBio, this crafty pathogen gets to work on its inventory of genes, slashing away until it finds a winning combination that can get it through the tough times. (I’ve written up other mBio papers about Candida here and here. I think I am gaining a grudging respect for this feisty fungus.)
In laboratory experiments, Forche et al. put Candida through the wringer by subjecting it to different physiologically stressful conditions, including increases in temperature (mimicking a moderate fever in a human), oxidative stress (mimicking the production of reactive oxygen species by immune cells) and antifungal stress (fluconazole, the most widely and commonly used antifungal drug). Like us, Candida is in possession of two sets of chromosomes, so it is heterozygous for many genes (it carries two different copies of them). If Candida shuffles its genes around, it inevitably loses some of these genes and finds itself with two identical copies of these genes where it once had two different copies. The authors call this “Loss of Heterozygosity”, or LOH.
Under stress, Candida shuffled its genes, and its LOH rates increased with increasing levels of stress. What’s more, the stressor determined what kind of shuffling went on: different stress conditions caused different types of LOH events. Many of the LOH events are identical to what has been seen in clinical settings or in Candida passaged through another mammalian host. The authors propose that the different types of LOH are related to the type of DNA damage inflicted by the stressors and that losing heterozygosity due to stress may be a way to ramp up adaptation to changing conditions. The feisty fungus wins again.