Candidalysin Is the Hemolytic Factor of Candida albicans .

produces an important virulence factor, the hypha-associated -derived secreted peptide toxin candidalysin, which is crucial for the establishment of mucosal and systemic infections. has also long been known to be hemolytic, yet the hemolytic factor has not been clearly identified. Here, we show that candidalysin is the hemolytic factor of . Its hemolytic activity is modulated by fragments of another peptide, P7. Hemolysis by candidalysin can be neutralized by the purinergic receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS). PPADS also affects candidalysin's ability to intercalate into synthetic membranes. We also describe the neutralization potential of two anti-candidalysin nanobodies, which are promising candidates for future anti- therapy. This work provides evidence that the historically proposed hemolytic factor of is in fact candidalysin and sheds more light on the complex roles of this toxin in biology and pathogenicity.