Manipal, March 02, 2026: Researchers at the Manipal Academy of Higher Education (MAHE), an Institution of Eminence Deemed to be University, have uncovered how the deadly airborne fungus Cryptococcus neoformans selectively attacks neurons in the human brain. The findings, published in Frontiers in Immunology, provide new insights into fungal meningitis and potential treatment approaches.
A Hidden Threat to the Brain
Cryptococcus neoformans is an opportunistic fungus that can cause life-threatening meningoencephalitis, especially in individuals with weakened immune systems. While it is known that the fungus releases a toxic molecule called glucuronoxylomannan (GXM) in the brain, the reason why certain brain cells are more vulnerable remained unclear.
The MAHE research team, led by Dr Dinesh Upadhya at the Centre for Molecular Neurosciences, Kasturba Medical College (KMC), used human brain organoids-lab-grown mini-brains derived from pluripotent stem cells-to replicate a human-like brain environment. “Our study shows that GXM preferentially targets neurons over other brain cells,” said Dr Upadhya. “Brain organoids allow us to understand microbial pathogenesis in a highly human-relevant system.”
Why Neurons Are Vulnerable
To investigate the mechanism behind this selective targeting, the researchers collaborated with scientists using the Schrödinger, Inc. Materials Science Suite for advanced molecular modelling. Atomistic simulations revealed that neurons are rich in a lipid called phosphatidylcholine (PC), which strongly attracts the fungal toxin GXM.
Once GXM binds to neuronal membranes, it reduces synaptophysin levels, a protein essential for neuronal communication. This disruption impairs brain signalling, explaining why neurons are more susceptible to infection and why the fungus causes meningitis. “This lipid-specific interaction clarifies the vulnerability of neurons and the pathogenesis of fungal meningitis,” explained Dr Vishukumar Aimanianda, co-investigator and Professor of Biochemistry at MAHE.
New Horizons for Treatment
By combining stem-cell biology with computational molecular modelling, the study sets a benchmark for using human brain organoids to study fungal infections. Researchers believe that understanding the molecular interactions of Cryptococcus neoformans could lead to targeted therapies that protect neurons and maintain brain function.
“Mapping these interactions at a molecular level opens new possibilities for developing treatments against fungal meningitis,” said Dr Kavitha Saravu, Professor of Infectious Diseases at MAHE. The research not only enhances understanding of fungal pathogenesis but also demonstrates the potential of cutting-edge organoid models in combating deadly brain infections.
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