Candidalysin Is the Hemolytic Factor of <i>Candida albicans</i>

oleh: Selene Mogavero, Sarah Höfs, Alexa N. Lauer, Rita Müller, Sascha Brunke, Stefanie Allert, Franziska Gerwien, Sabrina Groth, Edward Dolk, Duncan Wilson, Thomas Gutsmann, Bernhard Hube

Format: Article
Diterbitkan: MDPI AG 2022-12-01

Deskripsi

<i>Candida albicans</i> produces an important virulence factor, the hypha-associated <i>Ece1</i>-derived secreted peptide toxin candidalysin, which is crucial for the establishment of mucosal and systemic infections. <i>C. albicans</i> 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 <i>C. albicans</i>. Its hemolytic activity is modulated by fragments of another <i>Ece1</i> 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-<i>Candida</i> therapy. This work provides evidence that the historically proposed hemolytic factor of <i>C. albicans</i> is in fact candidalysin and sheds more light on the complex roles of this toxin in <i>C. albicans</i> biology and pathogenicity.