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 clearthat 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.
(2020) Candidalysin is a potent trigger of alarmin and antimicrobial peptide release in epithelial cells. Cells 9(3), 699.
(2020) Ahr1 and Tup1 contribute to the transcriptional control of virulence-associated genes in Candida albicans. mBio 11(2), e00206-20.
(2019) The Candida albicans exotoxin Candidalysin promotes alcohol-associated liver disease. J Hepatol 72(3), 391-400.
(2019) Cooperative role of MAPK pathways in the interaction of Candida albicans with the host Epithelium. Microorganisms 8(1), 48.
(2019) CARD9+ microglia promote antifungal immunity via IL-1β- and CXCL1-mediated neutrophil recruitment. Nat Immunol 20(5), 559-570.
(2019) Keeping Candida commensal: How lactobacilli antagonize pathogenicity of Candida albicans in an in vitro gut model. Dis Model Mech 12(9), dmm039719.
(2019) Candidalysin activates innate epithelial immune responses via epidermal growth factor receptor. Nat Commun 10(1), 2297.
(2019) Candidalysin: Discovery and function in Candida albicans infections. Curr Opin Microbiol 52, 100-109.
(2019) Host-pathogen interactions during female genital tract infections. Trends Microbiol 27(12), 982-996. (Review)
(2019) Candidalysin is required for neutrophil recruitment and virulence during systemic Candida albicans infection. J Infect Dis 220(9), 1477-1488.
(2019) Integrity under stress: Host membrane remodelling and damage by fungal pathogens. Cell Microbiol 21(4), e13016.
(2018) Candida albicans-induced epithelial damage mediates translocation through intestinal barriers. mBio 9(3), e00915.
(2018) The fungal peptide toxin Candidalysin activates the NLRP3 inflammasome and causes cytolysis in mononuclear phagocytes. Nat Commun 9(1), 4260.
(2018) Bis-guanylhydrazones as efficient anti-Candida compounds through DNA interaction. Appl Microbiol Biotechnol 102(4), 1889-1901.
(2018) Processing of Candida albicans Ece1p is critical for Candidalysin maturation and fungal virulence. mBio 9(1), e02178-17.
(2018) Candidalysin drives epithelial signaling, neutrophil recruitment, and immunopathology at the vaginal mucosa. Infect Immun 86(2), e00645-17.
(2016) Candidalysin is a fungal peptide toxin critical for mucosal infection. Nature 532(7597), 64-68.
(2016) The missing link between Candida albicans hyphal morphogenesis and host cell damage. PLOS Pathog 12(10), e1005867. (Review)
(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.
(2014) Distinct roles of Candida albicans-specific genes in host-pathogen interactions. Eukaryot Cell 13(8), 977-989.
(2011) The Candida albicans-specific gene EED1 encodes a key regulator of hyphal extension. PLOS One 6(4), e18394.
(2011) Host-pathogen interactions and virulence-associated genes during Candida albicans oral infections. Int J Med Microbiol 301(5), 417-422. (Review)
(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.
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