by Laura C. Ristow, Emma E. Blackburn, Andrew J. Jezewski, Xiaorong Lin, Damian J. Krysan Cryptococcus neoformans is an environmental pathogen that remodels its cellular physiology to survive within mammals and, in susceptible hosts, cause life-threatening meningoencephalitis. Of the many distinctions between the external environment and mammalian tissues, CO 2 concentration in the host is two orders of magnitude higher than in the environment and represents a critical stress for C. neoformans . C. neoformans strains that do not replicate at host CO 2 concentrations are less virulent in mouse models of infection, further supporting CO 2 tolerance as a virulence trait. To further understand the genetic determinants of C. neoformans CO 2 tolerance, we performed a near genome-wide screen for deletion mutants with altered CO 2 fitness using a competitive growth assay. A total of 301 of 4,692 deletion mutants showed altered CO 2 tolerance (245 reduced fitness; 56 increased fitness) demonstr