Scientists have uncovered a biological circuit that allows the deadly fungus Cryptococcus neoformans to transform into giant 'Titan cells', which help it evade the immune system and cause persistent infections. The research, led by CSIR-Centre for Cellular and Molecular Biology (CCMB) in Hyderabad, was published in the journal mBio.
The study found that the fungus uses its energy metabolism to activate a signaling pathway involving the protein PKA (protein kinase A). This pathway triggers the formation of Titan cells, which are enlarged cells that resist immune attack and antifungal drugs. The team identified a specific metabolic enzyme, pyruvate kinase, as a key regulator of this process.
According to the researchers, blocking this metabolic circuit could prevent Titan cell formation, offering a new therapeutic strategy against cryptococcosis, a disease that causes over 180,000 deaths annually worldwide, particularly in immunocompromised individuals.
βOur findings reveal a direct link between metabolism and virulence in this pathogen,β said Dr. K. V. S. Rao, senior author of the study. βTargeting this pathway could weaken the fungus and make it more susceptible to the immune system.β
The team plans to screen existing drugs that inhibit pyruvate kinase to test their effectiveness against C. neoformans in animal models.
