Image of the human fungal pathogen Candida albicans undergoing morphogenesis. The fungal cell wall is shown in light blue, and energy-producing mitochondria in red. Image credit: Shah et al. (CC BY 4.0)
Growing extra arms or tentacles, changing skin colour or texture – what sounds like the premise of a horror story is actually a common occurrence in nature. Many microscopic fungi can modify their shape to infect hosts and evade their immune defences. These organisms do not simply grow – they can alter their physical form depending on their environment. One moment, they are harmless, yeast-like cells, quietly living in the human gut; the next, they transform into long, thread-like filaments called hyphae that penetrate tissues and cause infections in animals and crops. Scientists call this extraordinary shape-shifting ability ‘fungal morphogenesis’.
While scientists have identified the genes involved in this process, the role of cellular metabolism has been less well established. Previous research suggests that the presence of glucose is important for fungal morphogenesis. But how this sugar influences this shape-shifting behaviour was not completely understood. Understanding what truly controls this process could uncover new ways to prevent harmful fungi from causing diseases in plants and animals.
To determine whether glucose merely supports fungal morphogenesis or truly drives this change, Shah et al. used baker’s yeast and a pathogenic yeast that causes thrush in humans. Both yeast species were grown under nitrogen-limited conditions, a known factor to trigger fungal morphogenesis. When glycolysis - the process that breaks down sugar molecules into energy - was blocked, neither species could shape-shift.
More detailed experiments showed that this was due to the need for glycolysis to produce sulfur-containing building blocks, such as amino acids, that support this transition. When these sulfur-containing building blocks were supplied from the outside, the fungi regained their ability to change shape – even under conditions compromising their ability to perform glycolysis.
This effect was observed in both yeast species, highlighting that this process must be conserved in potentially many yeast species. Blocking glycolysis disarms the pathogen, compromising its morphogenesis and rendering it vulnerable to host defence. This metabolic interference paves the way for a new class of precision antimicrobials that are both more potent in combating infections and less toxic to the infected host. Moreover, fungal morphogenesis has been implicated in causing resistance to existing antifungals. Therefore, targeting glycolysis will support the development of effective therapeutic strategies to increase the efficacy of existing antifungals.
