Scientists at the CSIR-Centre for Cellular and Molecular Biology (CCMB) have identified a previously unknown vulnerability in Cryptococcus neoformans, a deadly fungal pathogen, potentially opening up a new strategy to combat cryptococcal disease.The breakthrough centres on the fungus’s ability to form giant cells known as ‘Titan cells’, which help it evade the body’s immune defences. By targeting the metabolic processes that drive Titan cell formation, researchers believe it may be possible to weaken the fungus, enhance immune clearance and reduce the burden of cryptococcal meningitis.Cryptococcal meningitis affects more than 1.5 lakh people worldwide each year, including thousands in India, and has a high mortality rate. Unlike many fungal infections that remain confined to the skin, cryptococcal infection typically begins in the lungs and can spread through the bloodstream to the brain.While most fungal cells measure only a few micrometres in diameter, some enlarge into Titan cells, which are too large for immune cells to engulf and destroy effectively. This allows the fungus to evade immune attacks, survive in the body and establish persistent infections, scientists said.A team led by Sriram Varahan discovered a previously unknown biological circuit linking the fungus’s energy metabolism to a key cellular signalling system that enables Titan cell formation. Traditionally, metabolism has been viewed primarily as the process by which cells generate energy. The study, however, shows that it also acts as a regulatory system, influencing whether the fungus transforms into its more dangerous Titan-cell form.“Our findings show that metabolism is not merely supplying fuel. It is actively controlling the cellular signals that allow the fungus to transform into Titan cells,” said Mr Varahan. Researchers found that calcium, which serves as an important molecular messenger inside cells, activates calcineurin, a master signalling pathway that helps the fungus survive stressful conditions within the human body and develop into Titan cells.The study establishes, for the first time, a direct link between the fungus’s energy metabolism and calcium signalling in controlling Titan cell formation. Rather than operating independently, the two systems work as a coordinated biological network, enabling the pathogen to adapt and thrive within its host.The discovery could have significant therapeutic implications. Instead of focusing solely on killing the fungus, future treatments could aim to prevent Titan cell formation, effectively disarming one of the pathogen’s key disease-causing mechanisms before severe infection develops, scientists said. With invasive fungal pathogens causing hundreds of thousands of deaths annually and antifungal drug resistance on the rise, the finding offers a promising new direction for research, a press release said. Published - August 21, 2026 07:48 pm IST