Abstract
Candida albicans is a commensal fungus of humans but can cause infections, particularly in immunocompromised individuals, ranging from superficial to life-threatening systemic infections. The cell wall is the outermost layer of C. albicans that interacts with the host environment. Moreover, antimicrobial peptides (AMPs) are important components in innate immunity and play crucial roles in host defense. Our previous studies showed that the human AMP LL-37 binds to the cell wall of C. albicans, alters the cell wall integrity (CWI) and affects cell adhesion of this pathogen. In this study, we aimed to further investigate the molecular mechanisms underlying the C. albicans response to LL-37. We found that LL-37 causes cell wall stress, activates unfolded protein response (UPR) signaling related to the endoplasmic reticulum (ER), induces ER-derived reactive oxygen species and affects protein secretion. Interestingly, the deletion of the SFP1 gene encoding a transcription factor reduced C. albicans susceptibility to LL-37, which is cell wall-associated. Moreover, in the presence of LL-37, deletion of SFP1 attenuated the UPR pathway, upregulated oxidative stress responsive (OSR) genes and affected bovine serum albumin (BSA) degradation by secreted proteases. Therefore, these findings suggested that Sfp1 positively regulates cell wall integrity and ER homeostasis upon treatment with LL-37 and shed light on pathogen-host interactions.
Highlights
IntroductionAccepted: 28 September 2021Candida albicans is among the most common human fungal pathogens and can cause a broad range of infections, from superficial mucosal to life-threatening invasive candidiasis [1,2]
Accepted: 28 September 2021Candida albicans is among the most common human fungal pathogens and can cause a broad range of infections, from superficial mucosal to life-threatening invasive candidiasis [1,2]
Since the cell wall is the initial site for C. albicans to interact with its external environment, the structural and functional integrity of the cell wall is critical for cell survival under stress conditions
Summary
Accepted: 28 September 2021Candida albicans is among the most common human fungal pathogens and can cause a broad range of infections, from superficial mucosal to life-threatening invasive candidiasis [1,2]. The cell wall is the outermost layer of C. albicans and is mainly composed of proteins and fibrillary polysaccharides [3,4,5,6,7]. Mannan, β-glucan and chitin are the three major polysaccharides, and cell wall proteins are largely glycosylated with. The cell wall plays a critical role in maintaining cell integrity and survival and mediates the interaction between the pathogen and host environment [4,6,7]. C. albicans adhesion to abiotic medical devices and host cells and tissues mediated by the cell wall is essential for biofilm formation and mucosal infiltration [5,6,12]. Echinocandin antifungals interfere with cell wall formation [13]
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