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Scientists at the CSIR–Centre for Cellular and Molecular Biology (CCMB), Hyderabad, have uncovered a metabolic “switch” that helps fungi turn deadly. Controlling this switch, they say, could prevent fungi from becoming dangerous and help save lives.
According to CCMB, which made its findings public Saturday, fungal infections are quietly emerging as one of the most dangerous and underestimated threats of our time, and that this discovery could pave the way for promising new treatments. Researchers from the laboratory of Dr Sriram Varahan have identified how metabolic processes enable fungi to become harmful—and how this transformation might be stopped.
“Scientists may be able to disrupt the metabolic processes that fungi rely on for their survival,” Dr Varahan said. He added that “since these pathways are fundamental for fungal growth and shape-shifting, they may represent an ‘Achilles’ heel’ that is harder for fungi to escape through resistance”.
At a time when drug-resistant fungal infections are rising globally, the findings point to a powerful idea: stopping fungal infections may require cutting off the energy and nutrients that allow fungi to transform into harmful forms. “By targeting metabolism, we may be able to outsmart these shape-shifting invaders and develop safer, more effective antifungal therapies—protecting both human health and food security,” Dr Varahan said in a statement.
The study shows that fungi’s sugar metabolism controls the shape shift that drives infection.
“By looking at fungi through a metabolic lens, we uncovered what can be described as a previously hidden biological ‘short circuit’. We discovered a crucial connection between the process by which cells break down sugar to generate energy (called glycolysis) and the production of specific sulfur-containing amino acids,” Dr Varahan said.
Put simply, when fungi consume sugars rapidly, sugar breakdown also runs at high rates. This determines whether the cell can produce certain sulfur-based amino acids required to trigger invasive growth. As a result, fungal shape-shifting is not driven by genes alone—it is also fuelled and controlled by how fungi process nutrients.
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To demonstrate this, the team conducted laboratory experiments in which sugar breakdown was slowed in fungi. Under these conditions, the fungi remained trapped in a harmless, oval yeast form and were unable to transition into the invasive shapes associated with infection. However, when sulfur-containing amino acids were supplied externally, the fungi rapidly regained their ability to change shape. This “rescue” showed that these nutrients act as an essential on/off switch—without them, morphogenesis stalls; with them, invasive transformation resumes.
A remarkable “superpower” of fungi is their ability to change shape. They exist primarily in two forms—yeast (oval-shaped, about 5 microns in diameter) and filamentous (around 20–100 microns long). Yeast forms travel in search of suitable niches. Once anchored, they filament and take over the region.
When fungi enter the human body, they do so mainly in the yeast form. Inside the host, they encounter nutrient scarcity, temperature differences, and other microbes, all of which trigger filament formation. These filamentous forms are much harder for immune cells and medicines to eliminate.
For decades, scientists have known the genes and signalling pathways that instruct fungi to change shape. This study, however, reveals that shape-shifting is driven not only by gene networks but also by the fungus’s internal power supply—its metabolism.
The study also shows clear disease relevance.
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The researchers examined a strain of Candida albicans, a leading cause of fungal infections worldwide, that lacked a key sugar-breakdown enzyme. The strain became “metabolically crippled”, showing a reduced ability to undergo morphogenesis and a diminished capacity to survive attacks by macrophages, the body’s first line of immune defence. In mouse infection studies, this altered strain caused much milder disease than normal fungal strains. Disrupting fungal metabolism, the study found, reduced its ability to adapt, evade immunity, and establish infection.
According to CCMB, fungi are now responsible for a growing number of severe infections worldwide, contributing to rising hospitalisations and deaths, often overshadowed by viruses and bacteria. At the same time, fungal diseases are devastating crops, reducing yields and worsening food insecurity—creating a dual crisis for public health and agriculture.
Yet the ability to fight back is weakening. Antifungal drugs are far fewer than antibiotics, can be toxic, and are losing effectiveness due to antimicrobial resistance. Doctors and scientists are increasingly confronting a troubling reality: the pipeline of effective antifungal treatments is shrinking even as the threat expands. In this urgent global context, the findings of this study assume particular significance.
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