A NEW QUORUM SENSING MOLECULE IN C. NEOFORMANS, GIBBERELLIC ACID, INCREASES MELANIZATION IN THE PRESENCE OF TESTOSTERONE

Abstract

C. neoformans, a spore-producing pathogenic yeast, affects immunocompromised individuals causing meningoencephalitis. Once C. neoformans is introduced via the respiratory tract, it is engulfed by macrophages and other phagocytes. One of C. neoformans’s primary virulence factors is the pigment, melanin, which is produced in the cell wall and protects the yeast against UV radiation and oxidizing agents produced by macrophages during phagocytosis. To better understand the observed sex bias (3:1; male: female) in cryptococcosis infections, we determined the phenotype of various virulence factors in the presence of exogenous sex hormones. The data show a difference in melanization of C. neoformans cells in the presence of exogenous testosterone and estrogen, where C. neoformans melanizes faster in testosterone. Using a combination of RNA sequencing analysis and ELISA results, we have identified a new quorum sensing molecule, gibberellic acid (GA) in C. neoformans. These data suggest that this melanization difference in testosterone is due to increased production of GA, as GA is highly upregulated in the presence of testosterone. Thus, this may help explain the sex bias observed in C. neoformans infections.