Transcriptional control of environmental neutralization

Candida albicans and other Candida spp. grown on non-preferred carbon sources available in the host can actively neutralize the environmental pH from a very wide range of starting pHs (Vylkova et al., 2011). In C. albicans neutral pH is a potent stimulator of hyphal morphogenesis, a well-recognized virulence factor, and this fungal species is able to switch morphologies during transition from pH 4 to neutral. 

Stp2p, a transcription factor that regulates amino acid permease (AAP) genes, is required for environmental alkalinization in vitro, during macrophage phagocytosis, and for full virulence (Vylkova and Lorenz, 2014). Recently, we identified that another transcription factor, Ahr1p, is essential for pH modulation (Vylkova and Lorenz, 2017). Ahr1p plays role in adherence to biofilm and is predicted, but not verified, to control the expression of genes required for amino acid utilization, including AAPs (Askew et al., 2011). Thus, this project will investigate the connection between nutrient catabolic pathways and modulation of pH controlled by Ahr1p and Stp2p. In addition, we seek to identify the factors controlling hyphal morphogenesis during the process of environmental neutralization in vitro and within the host.

Candida albicans (green) engulfed by a macrophage (white blood cell). C. albicans promotes neutralization of the pH inside the macrophages, forms hyphae and escapes the human host cell later.