Subunits of adaptor protein complex-1 make distinct contributions to the virulence of Cryptococcus neoformans
Publication Date
Publication Journal
Author(s)
Kabir Bhalla, Eddy Sánchez-León, Yu-Hsuan Huang, Guanggan Hu, Anisha Neogi, Alba Torres-Cano, Oscar Zaragoza, Victoria French, Polina Beskrovnaya, Shweta Parmar, Melissa Lagace, Sophie Thanasack, E. Johan Foster, Pauline Johnson, Elitza Tocheva, James W. Kronstad
The fungal pathogen Cryptococcus neoformans can lead to life-threatening cryptococcal meningitis in people with compromised immune systems. In this study, the authors deleted the genes corresponding to each of the four subunits in C. neoforman's adaptor protein-1 (AP-1) complex, creating four fungal mutants. They found that the mutants were smaller, slower-growing, irregularly shaped, and less capable at surviving within macrophages. In mouse models, exposure to mutants lacking the large and medium subunits resulted in no evidence of disease, while exposure to the mutant lacking the small subunit resulted in granulomas in the lungs — structures in which the fungal infection is sequestered, but could later reactivate. These findings suggest that inhibiting one or more of the AP-1 subunits is a promising approach to combating C. neoformans infections in immunocompromised people.