Unlocking the role of fungal peptide cytotoxin candidalysin in candidiasis and non-candidiasis diseases.

Candida albicans is a commonly encountered opportunistic fungus that can cause both superficial discomforts and life-threatening invasive fungal infections. Ever-increasing reports have shown that C. albicans is also readily implicated in a set of metabolic and autoimmune diseases. Yeast-to-hypha transition is a hallmark of increased virulence and invasion of C. albicans, and candidalysin is the first peptide toxin secreted by C. albicans hyphae. Candidalysin contributes to fungal penetration across epithelial barrier via cytolytic activity, as well as the maintenance of commensalism and pathogenicity of Candida albicans. To specifically depict the role of candidalysin in multiple candidiasis and C. albicans associated infections, in this review, we focus on the recent advancements of candidalysin in oropharyngeal candidiasis (OPC), vulvovaginal candidiasis (VVC), disseminated candidaemia and sepsis. Meanwhile, we also pay close attention to the potential pathogenic mechanism of candidalysin in several C. albicans associated diseases including inflammatory bowel disease (IBD), asthma, Alzheimer's disease (AD) and alcohol-associated liver diseases (ALD). Based on these achievements, we propose a list of unresolved questions of interest for future investigation on biological functions and therapeutic potential of candidalysin in fungal infections caused by C. albicans. Unlocking the mode of action of candidalysin is beneficial for deep understanding of how C. albicans breaks through mucosal or blood brain barrier to colonize the niche via candidalysin and for rational design of fungal vaccine against candidalysin for clinical applications. Q1: Revision based on the comment 1 by Reviewer 1.