HYDERABAD: Scientists at CSIR-Centre for Cellular and Molecular Biology have uncovered a way to disarm one of fungi’s most dangerous traits — their ability to change shape and turn invasive.
Fungi survive in two main forms: a harmless, oval yeast form and a filamentous form that spreads aggressively inside the body. Once inside a host, many fungi switch to the filamentous shape to cope with nutrient stress, temperature changes and competition from other microbes. This transformation makes them harder for immune cells and medicines to eliminate, often leading to serious infections.
Until now, scientists believed this shape-shifting was driven mainly by genes and internal signalling pathways. The new study shows that metabolism — specifically how fungi process sugar — plays a decisive role.
Explaining the breakthrough, Dr Sriram Varahan, senior scientist, CCMB, says the team discovered a hidden link between sugar breakdown and the production of sulphur-containing amino acids. “When fungi consume sugars rapidly, glycolysis runs at high speed. This directly affects whether the cell can produce certain sulphur-based amino acids needed to trigger invasive growth,” he adds.
In other words, shape-shifting is not only genetically programmed, but fuelled by nutrient processing. To test this, researchers slowed sugar breakdown in fungal cells. Under these conditions, the fungi remained stuck in the harmless yeast form and could not become invasive. When sulphur-containing amino acids were added externally, the fungi quickly regained their ability to change shape.
The team also studied a strain of Candida albicans — a major cause of fungal infections worldwide — that lacked a key enzyme for sugar breakdown. The altered fungus was metabolically weakened, struggled to evade immune cells such as macrophages and caused much milder disease in mouse models compared to normal strains.
The findings suggest that disrupting fungal metabolism can limit its ability to adapt, escape immune defences and establish infection. “This opens a promising new direction for antifungal therapies,” Dr Varahan says, adding that targeting metabolic processes could offer an alternative to conventional drug strategies and help tackle rising antifungal resistance.