Investigating the role of the unfolded protein response in pH-induced beta-glucan unmasking in Candida albicans

Candida albicans is an opportunistic pathogen that colonises mucosal membranes in humans, such as the vaginal canal. C. albicans can switch morphologies, growing in yeast and hyphae forms, which is critical for virulence. In addition, C. albicans has been shown to remodel its cell wall, altering the host-pathogen interaction and contributing to fungal virulence. Several signalling pathways have been linked to environmental regulation of the cell wall, including the calcium and cAMP-dependent PKA signalling pathways. Recently, adaptations of C. albicans to acidic environments were shown to cause the underlying beta-glucan to become more exposed, inducing a strong proinflammatory immune response. However, the regulation of beta-glucan exposure in acidic environments is not understood. Here, it is identified that the activation of the unfolded protein response (UPR) is delayed in acidic environments. However, the deletion of key genes in the UPR pathway did not impact glucan exposure in response to an acidic environment but did affect general levels of glucan exposure. Activation of the UPR can also impact lipid composition. Mild SDS treatment mimicked glucan exposure to acidic environments, suggesting that acidic pH may include glucan exposure by altering lipid composition. Transmembrane proteins Wsc2 and Wsc4 potentially impact glucan exposure in an acidic environment. Wsc4 was then characterised to observe that it was not part of the cell wall integrity pathway and could form hyphae. The findings can contribute to a better understanding of the beta-glucan exposure mechanism in acidic environments and provide ways for scientists to find treatments.