CCMB team uncovers metabolic weakness in disease-causing fungi
HYDERABAD: Scientists at the CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad, have identified a key metabolic mechanism that enables disease-causing fungi to switch into invasive forms, offering a potential new target for antifungal therapies at a time of rising drug resistance.
Researchers led by Sriram Varahan have shown that the ability of fungi to change shape a process critical for infection is tightly linked to how they process sugar and produce certain sulphur-containing amino acids.
Fungal infections are increasingly recognised as a serious but underappreciated global threat, contributing to growing hospitalisations and deaths, while also damaging crops and worsening food insecurity. The challenge is compounded by a limited number of antifungal drugs and the rapid rise of antimicrobial resistance.
Fungi typically exist in two forms: a yeast form, which allows them to travel and spread, and a filamentous form, which enables them to invade tissues. When fungi enter the human body, they usually arrive as yeast cells. Stress conditions inside the host—such as nutrient scarcity, temperature changes and competition with other microbes trigger their transition into filamentous forms that are harder for immune cells and medicines to eliminate.
While earlier research focused on genes and signalling pathways that regulate this transformation, the CCMB study shows that metabolism plays a central role. “By looking at fungi through a metabolic lens, we uncovered a previously hidden biological short circuit,” Varahan said.
The team found that rapid sugar breakdown through glycolysis directly affects the production of specific sulphur-based amino acids required for invasive growth. When glycolysis was slowed in laboratory experiments, fungi remained locked in a harmless yeast form. Supplying these amino acids externally restored their ability to switch shape, confirming their role as a critical on-off switch for morphogenesis.
Weakened fungi show reduced virulence
The researchers tested their findings on a strain of Candida albicans, a leading cause of fungal infections worldwide. Strains lacking a key glycolytic enzyme were metabolically impaired, showed reduced ability to change shape, and were more vulnerable to attack by macrophages, the body’s first line of immune defence.
In mouse infection models, these altered strains caused significantly milder disease compared to normal strains, indicating that disrupting fungal metabolism limits the pathogen’s ability to adapt, evade immunity and establish infection.
According to Varahan, targeting such core metabolic pathways could offer a new antifungal strategy that is harder for fungi to bypass through resistance. “Since these pathways are fundamental for growth and shape-shifting, they may represent an Achilles’ heel,” he said.
The findings suggest that future antifungal therapies could focus on cutting off the energy and nutrients that allow fungi to become invasive, potentially leading to safer and more effective treatments while also helping protect food security.
