Is Involved in Resistance to 7-Aminocholesterol and Secretion of Fungal Proteins in .

() is a pathogenic yeast that is the leading cause of fungal meningitis in immunocompromised patients. Various virulence factors, such as the enzyme laccase and its product melanin, phospholipase, and capsular polysaccharide have been identified. During a screen of knockout mutants, the gene resistance to aminocholesterol 1 () was identified, the function of which is currently unknown in . Rta1 homologs in belong to a lipid-translocating exporter family of fungal proteins with transmembrane regions and confer resistance to the antimicrobial agent 7-aminocholesterol when overexpressed. To determine the role of in , the knock-out () and reconstituted () strains were created and phenotypically tested. was involved in resistance to 7-aminocholesterol, and also in exocyst complex component 3 (Sec6)-mediated secretion of urease, laccase, and the major capsule component, glucuronoxylomannan (GXM), which coincided with significantly smaller capsules in the and strains compared to the wild-type H99 strain. Furthermore, expression was reduced in a secretory 14 mutant () and increased in an RNAi Sec6 mutant. Transmission electron microscopy demonstrated vesicle accumulation inside the strain, predominantly near the cell membrane. Given that Rta1 is likely to be a transmembrane protein located at the plasma membrane, these data suggest that Rta1 may be involved in both secretion of various fungal virulence factors and resistance to 7-aminocholesterol in .