Scientists identify biological circuit behind ‘Titan cells’ of deadly fungus

HYDERABAD: A deadly fungus can employ its energy metabolism to activate a cellular pathway that helps it transform into giant cells, evade the body's immune system and establish persistent infections, scientists have identified.

Key points

• Researchers at CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad, have identified a biological circuit behind the formation of "Titan cells" in Cryptococcus neoformans.
• Researchers discovered that efficient glucose metabolism maintains calcium balance, activating the Calcineurin pathway that helps the fungus form Titan cells.
• While normal fungal cells are only a few micrometres throughout, some can enlarge dramatically and become giant 'Titan cells'.
• Scientists have known regarding Titan cells for almost two decades, but how they form remained unclear.
• "We uncovered an unexpected biological connection between the fungus's energy hub and one of its most important survival pathways, " Dr Varahan remarked.

Researchers at CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad, have identified a biological circuit behind the formation of "Titan cells" in Cryptococcus neoformans. It could offer a new way to treat cryptococcal infections. The fungus typically causes lung infections but can spread to the brain, causing meningitis that affects over 1, 50, 000 individuals globally each year.

Explaining how the fungus becomes harder to fight, Dr Sriram Varahan informed TNIE, "A key survival strategy of the fungus is its ability to change its size after entering the lungs. While normal fungal cells are only a few micrometres throughout, some can enlarge dramatically and become giant 'Titan cells'. These cells are a number of times larger than normal fungal cells and are much harder for immune cells to engulf and destroy."

Scientists have known regarding Titan cells for almost two decades, but how they form remained unclear. Researchers led by Dr Sriram Varahan at CCMB have now linked the fungus's energy metabolism to the cellular signalling system that drives Titan cell formation.

Researchers discovered that efficient glucose metabolism maintains calcium balance, activating the Calcineurin pathway that helps the fungus form Titan cells. Targeting this network could prevent Titan cell formation, making the fungus easier for the immune system to clear.

Taken together, the developments around scientists identify biological circuit behind 'Titan cells' of deadly fungus point to a situation that is still moving, and the coming days should bring more clarity.