Udupi: Researchers at Manipal Academy of Higher Education (MAHE) have uncovered how a deadly airborne fungus selectively attacks brain cells, offering new insight into fungal meningitis. The study, conducted at Centre for Molecular Neurosciences, Kasturba Medical College (KMC), Manipal, explains why Cryptococcus neoformans, a life-threatening pathogen, specifically targets neurons. The findings were recently published in Frontiers in Immunology.Cryptococcus neoformans is an airborne fungus that can cause fatal meningoencephalitis, especially in people with weakened immune systems. It’s been found that once it enters the brain, the fungus releases a toxic molecule called glucuronoxylomannan (GXM). However, the reason certain brain cells are more vulnerable remained unclear.The MAHE team, led by Dinesh Upadhya, used human brain organoids—laboratory-grown mini-brain models—to recreate a human-like brain environment. “Our study shows that GXM preferentially targets neurons over other brain cells,” said Upadhya. “Brain organoids allow us to understand microbial pathogenesis in a highly human-relevant system.”To probe this selective targeting, researchers used advanced molecular modelling in collaboration with scientists working with the Schrödinger, Inc. Materials Science Suite. Atomistic simulations helped create detailed computational models of brain cell membranes. They found that neurons are rich in phosphatidylcholine (PC), a lipid molecule strongly attracted to the fungal toxin GXM. This interaction effectively guides the toxin towards neurons.Once attached, GXM sharply reduced synaptophysin levels, a protein vital for neuronal communication, indicating direct disruption of brain signalling. “This lipid-specific interaction explains why neurons are preferentially affected, leading to meningitis,” said Vishukumar Aimanianda, professor of biochemistry at MAHE and co-investigator.By identifying the molecular basis of this targeting, researchers say the findings could help shape more focused therapies. “Understanding these interactions at a molecular level opens new avenues for developing treatments aimed at protecting brain function,” said Kavitha Saravu, professor of infectious diseases at MAHE.
