Hyderabad Scientists Uncover Metabolic Trigger Behind Deadly Fungal Infections
Scientists at Hyderabad's CSIR–Centre for Cellular and Molecular Biology (CCMB) have made a groundbreaking discovery that could revolutionize the fight against deadly fungal infections. Researchers from Dr Sriram Varahan's laboratory have identified a crucial metabolic "switch" that enables fungi to transform into harmful, invasive forms.
The Hidden Biological Short Circuit
According to the findings made public on Saturday, fungal infections represent one of the most dangerous and underestimated threats of our time. Dr Varahan's team discovered what they describe as a "previously hidden biological short circuit" connecting sugar metabolism to fungal shape-shifting.
The research reveals that when fungi consume sugars rapidly, their sugar breakdown process (glycolysis) runs at high rates. This determines whether the cell can produce specific sulfur-containing amino acids required to trigger invasive growth. Essentially, fungal shape-shifting is not driven by genes alone—it is also fueled and controlled by how fungi process nutrients.
Laboratory Experiments Demonstrate Control Mechanism
The research team conducted laboratory experiments that demonstrated how controlling this metabolic switch could prevent fungal infections:
- When sugar breakdown was slowed in fungi, they remained trapped in a harmless, oval yeast form
- These fungi were unable to transition into the invasive shapes associated with infection
- When sulfur-containing amino acids were supplied externally, the fungi rapidly regained their ability to change shape
This "rescue" experiment showed that these nutrients act as an essential on/off switch—without them, morphogenesis stalls; with them, invasive transformation resumes.
Fungal Shape-Shifting: A Dangerous Superpower
Fungi possess a remarkable ability to change shape, existing primarily in two forms:
- Yeast form (oval-shaped, about 5 microns in diameter) that travels in search of suitable niches
- Filamentous form (around 20–100 microns long) that takes over regions once anchored
When fungi enter the human body, they typically do so 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.
Disease Relevance and Practical Implications
The study examined Candida albicans, a leading cause of fungal infections worldwide. Researchers worked with a strain that lacked a key sugar-breakdown enzyme, making it "metabolically crippled." This strain showed:
- Reduced ability to undergo morphogenesis
- Diminished capacity to survive attacks by macrophages (the body's first line of immune defense)
- In mouse infection studies, caused much milder disease than normal fungal strains
"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 stated.
The Growing Global Threat
Fungi are now responsible for a growing number of severe infections worldwide, contributing to rising hospitalizations and deaths. Simultaneously, fungal diseases are devastating crops, reducing yields, and worsening food insecurity—creating a dual crisis for public health and agriculture.
The ability to fight back is weakening as antifungal drugs are far fewer than antibiotics, can be toxic, and are losing effectiveness due to antimicrobial resistance. Doctors and scientists face a troubling reality: the pipeline of effective antifungal treatments is shrinking even as the threat expands.
Dr Varahan emphasized 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."
This discovery comes at a critical time when drug-resistant fungal infections are rising globally. The findings point to a powerful approach: stopping fungal infections may require cutting off the energy and nutrients that allow fungi to transform into harmful forms. The Hyderabad research offers hope for developing new treatments that target fungal metabolism rather than just genetic pathways.
