Candidalysin at the epithelial-systemic interface: mechanistic evidence, critical-care relevance, and translational opportunities in invasive candidiasis.

Invasive candidiasis remains a stubborn source of morbidity and mortality in critically ill and immunocompromised patients. One reason progress has been slow is that the route from epithelial colonization to bloodstream or deep-organ infection is still described with more confidence than the evidence often allows. Candidalysin, a 31-amino-acid amphipathic peptide released from the Ece1 precursor by Candida albicans hyphae, is well established as a driver of epithelial damage and mucosal immune activation. Its contribution to invasive disease is far less certain. Recent work has broadened the molecular framework for candidalysin biology. Host-binding studies have identified sulfated glycosaminoglycans and other candidate partners. Biophysical studies have refined models of peptide polymerization, membrane insertion, and host membrane repair. Infection models have linked candidalysin to intestinal epithelial barrier failure, catheter persistence, macrophage escape, neutrophil remodeling, commensal fitness, and protective Th17 immunity. These observations sit at different distances from human invasive candidiasis: some are biochemical or cell-based, some are supported by organotypic or animal models, and only a small subset currently has human diagnostic or clinical correlation. In this review, we separate these evidence layers and argue that candidalysin should be treated as a candidate biomarker or adjunctive target for selected toxin-producing Candida albicans infections, not as a general explanation for invasive candidiasis.