Damage to the host

The mechanism by which Candida albicans damages host cells has been considered to be multi-factorial, and presumed to rely on a combination of adhesion, invasion, hyphal extension, turgor pressure and the secretion of hydrolytic enzymes. Although toxin production by C. albicans has long been postulated and the culture supernatants of C. albicans hyphae have been shown to exhibit haemolytic activity, the mechanism underlying C. albicans’ ability to lyse host cells has remained elusive. It is clear that hyphae are crucial for adhesion, invasion and damage. Thus, host cell damage is caused by hyphae and/or a hyphal associated factor. However, the exact molecular mechanisms by which C. albicans destroys these host cells has remained enigmatic.

We have identified a peptide toxin, secreted by C. albicans, which has remarkable similarities with melittin – the major component of bee venom. By deleting the encoding gene and in vitro synthesis of the fragment, we have shown that this peptide is, in itself, essential and sufficient for the lysis of host cells. In collaboration with Dr Julian Naglik, Kings College London/UK and other cooperation partners, we elucidated intracellular processing of the Ece1 polyprotein into different peptides including the secreted, damage-mediating candidalysin. Ongoing work and cooperations, e.g. with Dr Thomas Gutsmann, Forschungszentrum Borstel/Germany, now examine the exact mechanism by which this potent C. albicans cytolysin disrupts host cell integrity and investigate the role of non-candidalysin Ece1 peptides (NCEPs, PI-II, IV-VIII) for the biology of C. albicans and its interaction with the host.


Stefanie Allert
Rita Müller


Richardson JP, Mogavero S, Moyes DL, Blagojevic M, Krüger T, Verma AH, Coleman BM, De La Cruz Diaz J, Schulz D, Ponde NO, Carrano G, Kniemeyer O, Wilson D, Bader O, Enoiu SI, Ho J, Kichik N, Gaffen SL, Hube B, Naglik JR (2018) Processing of Candida albicans Ece1p is critical for Candidalysin maturation and fungal virulence. mBio 9(1), e02178-17.
Richardson JP, Willems HME, Moyes DL, Shoaie S, Barker KS, Tan SL, Palmer GE, Hube B, Naglik JR, Peters BM (2018) Candidalysin drives epithelial signaling, neutrophil recruitment, and immunopathology at the vaginal mucosa. Infect Immun 86(2), e00645-17.
Moyes DL*, Wilson D*, Richardson JP*, Mogavero S*, Tang SX, Wernecke J, Höfs S, Gratacap RL, Robbins J, Runglall M, Murciano C, Blagojevic M, Thavaraj S, Förster TM, Hebecker B, Kasper L, Vizcay G, Iancu SI, Kichik N, Häder A, Kurzai O, Luo T, Krüger T, Kniemeyer O, Cota E, Bader O, Wheeler RT, Gutsmann T, Hube B, Naglik JR (2016) Candidalysin is a fungal peptide toxin critical for mucosal infection. Nature 532(7597), 64-68.
Wilson D, Naglik JR, Hube B (2016) The missing link between Candida albicans hyphal morphogenesis and host cell damage. PLOS Pathog 12(10), e1005867. (Review)
Mech F, Wilson D, Lehnert T, Hube B, Figge MT (2014) Epithelial invasion outcompetes hypha development during Candida albicans infection as revealed by an image-based systems biology approach. Cytometry A 85(2), 126-139.
Wilson D, Mayer FL, Miramón P, Citiulo F, Slesiona S, Jacobsen ID, Hube B (2014) Distinct roles of Candida albicans-specific genes in host-pathogen interactions. Eukaryot Cell 13(8), 977-989.
Martin R, Moran GP, Jacobsen ID, Heyken A, Domey J, Sullivan DJ, Kurzai O, Hube B (2011) The Candida albicans-specific gene EED1 encodes a key regulator of hyphal extension. PLOS One 6(4), e18394.
Martin R, Wächtler B, Schaller M, Wilson D, Hube B (2011) Host-pathogen interactions and virulence-associated genes during Candida albicans oral infections. Int J Med Microbiol 301(5), 417-422. (Review)
Wächtler B, Wilson D, Haedicke K, Dalle F, Hube B (2011) From attachment to damage: defined genes of Candida albicans mediate adhesion, invasion and damage during interaction with oral epithelial cells. PLOS One 6(2), e17046.