Amino acid sensing and filamentous growth in the human pathogen Candida albicans

Candida albicans is an important human pathogen that displays a remarkable ability to detect changes in its environment and to appropriately respond by changing its cell morphology and physiology. Serum and amino acid-based media are known to induce filamentous growth in this organism. However, the mechanism by which amino acids induce filamentation is not yet known. Here, we describe the identification and characterization of the primary amino acid sensor, Csy1p, of C. albicans. We show that Csy1p plays an important role in amino acid sensing, filamentation, and virulence. Loss of Csy1p results in a lack of amino acid-mediated activation of amino acid transport and lack of induction of transcription of specific amino acid permease genes. Furthermore, csy1Δ/csy1Δ strain, lacking Csy1p, is defective in filamentation, displays altered colony morphology in serum and amino acid-based media, reduced expression of filamentation and virulence specific genes, and attenuated virulence. We also demonstrated that sensing of amino acids by Csy1p results in the activation of two independent signaling pathways, the Csy1p-Ctp1p pathway that controls expression of amino acid permease genes and a new Csy1p-Efg1p morphogenetic pathway that controls yeast-hyphae morphogenesis. These data provided the first evidence that C. albicans utilizes the amino acid sensor Csy1p to probe its environment, coordinate its nutritional requirement and determine its morphological state and pathogenicity.