An ER packaging chaperone determines the amino acid uptake capacity and virulence of Candida albicans

The Candida albicans CSH3 gene encodes a functional and structural homologue of Shr3p, a yeast protein that is specifically required for proper uptake and sensing of extracellular amino acids in Saccharomyces cerevisiae. A Candida csh3Delta/csh3Delta null mutant has a reduced capacity to take up amino acids, and is unable to switch morphologies on solid and in liquid media in response to inducing amino acids. CSH3/csh3Delta heterozygous strains display normal amino acid induced morphological switching. However, although heterozygous cells apparently sense and properly react to amino acid induced signals they cannot take up amino acids at wild-type rates. Strikingly, both CSH3/csh3Delta heterozygous and csh3Delta/csh3Delta homozygous strains are unable to efficiently mount virulent infections in a mouse model. The haploinsufficiency phenotypes indicate that both CSH3 alleles contribute to maintain high-capacity amino acid uptake in wild-type strains. These results strongly suggest that C. albicans cells use amino acids, presumably as nitrogen sources, during growth in mammalian hosts.