Adaptation of Candida albicans to osmotic and oxidative stress drives innate immune evasion through distinct pathways

Candida albicans is an opportunistic fungal pathogen causing superficial and systemic infections in humans. To survive in the host, C. albicans must evade attack from the human immune system, which it achieves through various mechanisms such as the remodelling of its cell wall and the recruitment of host regulatory factors, such as Factor H. The fungus regulates its immune evasion mechanisms in response to environmental factors such as lactate, hypoxia and iron limitation, which induce masking of cell wall β glucan, as well as oestrogen, which promotes the recruitment of Factor H to the cell surface through the action of the Factor H binding protein Gpd2. Here, we provide evidence that oxidative and osmotic stress are also environmental cues regulating immune evasion. To explore the mechanisms underlying these responses, as well as the previously described response to oestrogen, molecular and cellular assays are employed to measure factors such as gene expression, protein expression, protein localisation, cell wall composition and Factor H recruitment, in both wild type and genetically modified strains. It is demonstrated that, similarly to the response to oestrogen, oxidative stress induced immune evasion requires Gpd2. However, unlike the oestrogen response, Gpd2 is not required for Factor H recruitment, meaning it must play another role, such as promoting Factor H activity. The response to osmotic stress, on the other hand, appears entirely novel. Although the transcription factor Cap1 has been identified as an essential component of this response, the mechanisms driving evasion under this condition remain elusive. The data described here contributes to the growing body of evidence that C. albicans possesses a varied armoury of immune evasion mechanisms, which are tightly regulated in response to environmental stimuli. Increasing the understanding of these mechanisms, and the factors driving them, is vital for informing the development of additional drugs and treatment strategies.