Fierce Fungi Friend-making Fury

We tend to think of microbial species in a simplistic way as either our friends or our enemies. One recent paper questioned this perspective by investigating whether a microbial enemy could be converted to be a friend. This study focused on Candida albicans,  a fungus that can live on our skin and in other locations on our bodies. C. albicans infections can be particularly nasty in individuals with weakened immune systems. Overgrowth of C. albicans is called candidiasis. Candidiasis in the oral cavity is known as oral thrush, whereas in the vaginal tract it is commonly referred to as a yeast infection. This fungus grows in two main forms: as individual yeast cells and as long chains of cells called “hyphae”. Interestingly, C. albicans is typically in the hyphal form when causing an infection. 

The two major forms of Candida albicans. Figure adapted from Kabir et al. 2012. ISRN Microbiology.

In this study, the researchers investigated  how C. albicans  changes when it adapts to the mouse gut. To begin, they first had to ensure that the mice had no bacteria in their guts so they used broad-spectrum antibiotics. They then fed C. albicans to the mice so it could re-populate the gut. The researchers then isolated fungus from stool in the first set of mice and used the fungus to inoculate a second set of mice. The pattern continued as they isolated fungus from the second set of mice and used it to inoculate a third set. After 10 weeks they compared the phenotype (the observed traits) and genotype (the potential within the DNA) between the initial and gut-adapted C. albicans strains. They identified that in almost all cases the ability to form hyphae was lost in gut-adapted strains. But why would the fungus lose the ability to form hyphae? It turns out that the hyphae are mainly advantageous in the gut when C. albicans is fighting commensal bacteria. After these bacteria were wiped out by antibiotics expressing the hyphae form of C. albicans was a slight disadvantage compared to the yeast form. Thus, the loss of the hyphal form of the fungus was an adaptation to its new environment that lacked competitors. Usually when we think of adaptations we think of the gain of functions, like claws, teeth, flight, etc. In this case the  adaptive benefit was conferred by the loss of a function! 

So, the fungi adapted to the gut – does that make them friendly? To answer that question the researchers first demonstrated that the gut-adapted fungi were no longer dangerous. Usually when C. albicans is injected into the bloodstream of mice they die after a couple of days. The researchers showed that the original C. albicans strain was indeed lethal in mice. However, injecting mice with the gut-adapted C. albicans had little negative effect on them. Furthermore, injecting mice with the gut-adapted C. albicans primed their immune systems and the mice were better able to fight off subsequent infections. Due to this benefit to the host the researchers argued that the gut-adapted C. albicans evolved from pathogens to mutualists: from enemies to friends. 

This result highlights that the relationship between organisms isn’t set in stone. As the environment changes (such as antibiotics wiping out bacterial competitors) the best strategy for a colonizing microbe also changes. 

Summary written by: Gavin Douglas

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