The tricarboxylic acid cycle, cell wall integrity pathway, cytokinesis and intracellular pH homeostasis are involved in the sensitivity of Candida albicans cells to high levels of extracellular calcium.

Through a genetic screen we have identified 21 genes whose inactivation renders Candida albicans cells sensitive to high levels of extracellular calcium. These genes are involved in the tricarboxylic acid cycle, cell wall integrity pathway, cytokinesis, intracellular pH homeostasis, magnesium transport, as well as DNA damage response and repair processes. The calcium sensitivity due to inactivation of nine of these genes can be partially or completely suppressed by cyclosporine A, an inhibitor of calcineurin. Therefore, the calcium sensitivity of nearly a half of these 21 mutations is at least partially due to the activation of calcium/calcineurin signaling. Our work provides a basis for further understanding the regulation of calcium homeostasis in this important human fungal pathogen.