CCMB scientists identify metabolism as new target for antifungal therapies

Fungal infections are among the most underestimated health threats worldwide, contributing to rising hospitalizations and deaths. Beyond human health, fungi also devastate crops, reduce yields, and worsen food insecurity — creating a dual crisis for both public health and agriculture.

Now, researchers at the CSIR–Centre for Cellular and Molecular Biology (CCMB) in Hyderabad have uncovered a significant insight into how fungi become dangerous in the first place. Their findings point to a promising new pathway for developing antifungal therapies by targeting fungal metabolism rather than only gene networks.

Fungi can exist in two forms

Led by scientist Sriram Varahan, the study reveals that a fungus’s ability to switch shapes — a key factor in its infectiousness — is driven not only by genetic signals but also by its internal energy‑generating processes. Fungi can exist in two major forms: a small, oval yeast form and a larger filamentous form.

(From left) Siddhi Gupta, Dhrumi Shah, Sriram Varahan and Sudharsan M
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How yeast travels to transform into filamentous form

The yeast form travels through the host environment searching for a niche to anchor. Once it finds one, it transforms into filaments, allowing it to invade tissues aggressively. Inside the human body, fungi encounter nutrient scarcity, temperature shifts, and competing microbes. These stresses typically trigger their transformation into the filamentous form, which is much harder for both immune cells and medicines to eliminate.

A key link needed for fungal invasion

While earlier studies have focused heavily on genes that control these shape changes, the CCMB research highlights metabolism as a critical, previously overlooked driver. “We uncovered what can be described as a hidden biological short circuit,” said Mr. Varahan. “We found a direct link between glycolysis — the process of breaking down sugars — and the production of sulfur‑containing amino acids needed for fungal invasion.”

Why fungi need sugars?

When fungi rapidly consume sugars, they generate the sulfur‑based amino acids required to initiate invasive filament formation. The team tested what happens when sugar breakdown is slowed. In these conditions, the fungi remained trapped in their harmless yeast form and could not transition into the disease‑causing state. However, when sulfur‑containing amino acids were added externally, the fungi quickly regained their invasive ability.

The researchers studied a Candida albicans strain lacking a key enzyme for sugar breakdown and found it to be “metabolically crippled.” It struggled to change shape, was easily destroyed by immune cells, and caused only mild disease in mouse models.

‘Achilles’ heel’ of fungal pathogens

These findings suggest that interfering with fungal metabolism may be the ‘Achilles’ heel’ of fungal pathogens. Mr. Varahan notes that with drug‑resistant fungal infections on the rise, targeting metabolism could lead to safer, more effective antifungal therapies— benefiting both human health and agricultural security.