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 shown to exhibit haemolytic activity, the mechanism underlying C. albicans ability to lyse host cells has remained elusive. It is clear, however, that hyphae are essential for adhesion, invasion and damage. Thus, 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 Dr Thomas Gutsmann, Forschungszentrum Borstel/Germany, we are now examining the mechanism by which this potent C. albicans cytolysin disrupts host cell integrity.
(2019) CARD9+ microglia promote antifungal immunity via IL-1β- and CXCL1-mediated neutrophil recruitment. Nat Immunol 20(5), 559-570.
(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), e00915-18.
(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), pii: e02178-17.
(2017) Candidalysin drives epithelial signaling, neutrophil recruitment, and immunopathology at the vaginal mucosa. Infect Immun , pii: IAI.00645-17.
(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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Dr. Selene Mogavero
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