GSE130948
Re-masking of fungal cell wall PAMPs in response to environmental pH is regulated by multiple processes
Candida albicans is a commensal yeast of the human gut, which is tolerated by the immune system, but has the potential to become an opportunistic pathogen. One way in which C. albicans achieves this duality is through the concealing, or exposure of cell wall associated pathogen-associated molecular patterns (PAMPs) in response to host derived environment cues (pH, hypoxia, lactate). This cell wall remodelling allows C. albicans to evade or hyperactivate the host's innate immune responses leading to disease. Previously we identified that adaptation of C. albicans to acidic environments, conditions encountered during colonisation of the female reproductive tract, induce significant cell wall remodelling resulting in the exposure of two key fungal PAMPs (glucan and chitin). Here we report that this pH-dependent cell wall remodelling is a highly dynamic process, requiring periods of both cell wall unmasking, with peak PAMP exposure occurring between 2-4 hrs, followed by subsequent PAMP remasking. b-glucan remasking was mediated via the cell density dependent fungal quorum sensing molecule farnesol, while chitin remasking was mediated via a small, heat-stable, non-proteinaceous secreted molecule(s). Transcript profiling identified a core set of 42 genes significantly regulated by pH over time, and linked the transcription factor Efg1p to being the main regulator of chitin exposure through regulation of CHT2. This dynamic cell wall remodelling, influenced innate immune recognition of C. albicans, suggesting that during infection C. albicans can manipulate the host innate immune responses. Overall design: Transcriptional response of C. albicans (SC5314) to YPD buffered at pH4 or pH6 over a 8h period.