The SPS Amino Acid Sensor Mediates Nutrient Acquisition and Immune Evasion in Candida Albicans

Candida albicans is well adapted to its host and is able to sense and respond to the nutrients available within. We have shown that C. albicans avidly utilizes amino acids as a carbon source, which allows this opportunistic pathogen to neutralize acidic environments, including the macrophage phagosome. The transcription factor Stp2 is a key regulator of this phenomenon, and we sought to understand the mechanism of activation of Stp2, focusing on the SPS sensor system previously characterized for its role in nitrogen acquisition. We generated deletion mutants of the three components, SSY1, PTR3 and SSY5 and demonstrated that these strains utilize amino acids poorly as carbon source, cannot neutralize the medium in response to these nutrients, and have reduced ammonia release. Exogenous amino acids rapidly induce proteolytic processing of Stp2 and nuclear translocation in an SPS-dependent manner. A truncated version of Stp2, lacking the amino terminal nuclear exclusion domain, could suppress the growth and pH neutralization defects of the SPS mutants. We showed that the SPS system is required for normal resistance of C. albicans to macrophages and that mutants defective in this system reside in more acidic phagosomes compared with wild type cells; however, a more equivocal contribution was observed in the murine model of disseminated candidiasis. Taken together, these results indicate that the SPS system is activated under carbon starvation conditions resembling host environments, regulating Stp2 functions necessary for amino acid catabolism and normal interactions with innate immune cells.