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Volume 14
Issue 12
10.3390/toxins14120874
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Article

Candidalysin Is the Hemolytic Factor of Candida albicans

by
Selene Mogavero
1,*,
Sarah Höfs
1,
Alexa N. Lauer
1,2,
Rita Müller
1,
Sascha Brunke
1,
Stefanie Allert
1,
Franziska Gerwien
1,
Sabrina Groth
3,
Edward Dolk
4,
Duncan Wilson
5,
Thomas Gutsmann
3 and
Bernhard Hube
1,2,*
1
Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology–Hans Knoell Institute (HKI), 07745 Jena, Germany
2
Institute of Microbiology, Friedrich Schiller University, 07745 Jena, Germany
3
Research Center Borstel, Division of Biophysics, 23845 Borstel, Germany
4
QVQ B.V., 3584 CL Utrecht, The Netherlands
5
Medical Research Council Centre for Medical Mycology, University of Exeter, Exeter EX4 4RN, UK
*
Authors to whom correspondence should be addressed.
Toxins 2022, 14(12), 874; https://doi.org/10.3390/toxins14120874
Submission received: 21 November 2022 / Revised: 7 December 2022 / Accepted: 13 December 2022 / Published: 15 December 2022
(This article belongs to the Section Mycotoxins)
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Abstract

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

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MDPI and ACS Style

Mogavero, S.; Höfs, S.; Lauer, A.N.; Müller, R.; Brunke, S.; Allert, S.; Gerwien, F.; Groth, S.; Dolk, E.; Wilson, D.; et al. Candidalysin Is the Hemolytic Factor of Candida albicans. Toxins 2022, 14, 874. https://doi.org/10.3390/toxins14120874

AMA Style

Mogavero S, Höfs S, Lauer AN, Müller R, Brunke S, Allert S, Gerwien F, Groth S, Dolk E, Wilson D, et al. Candidalysin Is the Hemolytic Factor of Candida albicans. Toxins. 2022; 14(12):874. https://doi.org/10.3390/toxins14120874

Chicago/Turabian Style

Mogavero, Selene, Sarah Höfs, Alexa N. Lauer, Rita Müller, Sascha Brunke, Stefanie Allert, Franziska Gerwien, Sabrina Groth, Edward Dolk, Duncan Wilson, and et al. 2022. "Candidalysin Is the Hemolytic Factor of Candida albicans" Toxins 14, no. 12: 874. https://doi.org/10.3390/toxins14120874

APA Style

Mogavero, S., Höfs, S., Lauer, A. N., Müller, R., Brunke, S., Allert, S., Gerwien, F., Groth, S., Dolk, E., Wilson, D., Gutsmann, T., & Hube, B. (2022). Candidalysin Is the Hemolytic Factor of Candida albicans. Toxins, 14(12), 874. https://doi.org/10.3390/toxins14120874

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