Wirtsschädigung
Candida albicans hat eine Vielzahl von Mechanismen zur Verfügung, um den Wirt zu schädigen. Man nimmt an, dass die Kombination von Adhäsion, Invasion, Hyphenbildung und -verlängerung, Turgordruck und Sekretion von hydrolytischen Enzymen entscheidend für die Schädigung ist. Zusätzlich wurde schon lange vermutet, dass C. albicans zur Bildung von Toxinen (Zellgiften) in der Lage ist. Tatsächlich zeigt der Überstand von C. albicans-Hyphenkulturen eine hämolytische (blutzellzerstörende) Aktivität. Der molekulare Mechanismus, mit dem C. albicans Wirtszellen zerstört, war aber bislang unbekannt. Klar war nur, dass dieser Mechanismus mit der Hyphenbildung in Zusammenhang stehen muss, da nur Hyphen zu Adhesion, Invasion und Schädigung von Wirtszellen in der Lage sind.
Wir konnten ein von C. albicans sezerniertes Peptid identifizieren, das eine erstaunliche Ähnlichkeit zu dem Bienengift Melittin aufweist. Durch Deletion dieses Gens und über eine künstliche Synthese des Peptids konnten wir zeigen, dass dieses Peptid nötig und alleine ausreichend für die Zerstörung von Wirtszellen ist. In enger Koopereration mit Dr. Julian Naglik (Kings College London) und Dr. Thomas Gutsmann (Forschungszentrum Borstel) untersuchen wir nun den genauen Mechanismus, mit dem dieses neuartige, hochwirksame C. albicans-Toxin die Wirtszellintegrität zerstören kann.

(2019) Recent trends in molecular diagnostics of yeast infections: from PCR to NGS. FEMS Microbiol Rev 43(5), 517-547. Details PubMed
(2019) The Candida albicans exotoxin Candidalysin promotes alcohol-associated liver disease. J Hepatol , Details PubMed
(2019) The Itaconate Pathway Is a Central Regulatory Node Linking Innate Immune Tolerance and Trained Immunity. Cell Metab [Accepted] Details PubMed
(2019) CARD9+ microglia promote antifungal immunity via IL-1β- and CXCL1-mediated neutrophil recruitment. Nat Immunol 20(5), 559-570. Details PubMed
(2019) Disruption of membrane integrity by the bacteria-derived antifungal jagaricin. Antimicrob Agents Chemother 63(9), pii: e00707-19. Details PubMed
(2019) Keeping Candida commensal - How lactobacilli antagonize pathogenicity of Candida albicans in an in vitro gut model. Dis Model Mech 12(9), pii: dmm039719. Details PubMed
(2019) Frontline Science: Endotoxin-induced immunotolerance is associated with loss of monocyte metabolic plasticity and reduction of oxidative burst. J Leukoc Biol [Accepted] Details PubMed
(2019) Candidalysin activates innate epithelial immune responses via epidermal growth factor receptor. Nat Commun 10(1), 2297. Details PubMed
(2019) Effects of histatin 5 modifications on antifungal activity and kinetics of proteolysis. Protein Sci , Details PubMed
(2019) RNAi as a Tool to Study Virulence in the Pathogenic Yeast Candida glabrata. Front Microbiol 10, 1679. Details PubMed
(2019) A Genome-Wide Functional Genomics Approach Identifies Susceptibility Pathways to Fungal Bloodstream Infection in Humans. J Infect Dis [Accepted] Details PubMed
(2019) A systems genomics approach identifies SIGLEC15 as a susceptibility factor in recurrent vulvovaginal candidiasis. Sci Transl Med [Accepted] Details PubMed
(2019) Candidalysin: discovery and function in Candida albicans infections. Curr Opin Microbiol 52, 100-109. Details PubMed
(2019) Host-Pathogen Interactions during Female Genital Tract Infections. Trends Microbiol , pii: S0966-842X(19)30190-8. (Review) Details PubMed
(2019) Candidalysin is required for neutrophil recruitment and virulence during systemic Candida albicans infection. J Infect Dis 220(9), 1477-1488. Details PubMed
(2019) Integrity under stress: Host membrane remodelling and damage by fungal pathogens. Cell Microbiol 21(4), e13016. Details PubMed Open Access
(2018) Candida albicans-induced epithelial damage mediates translocation through intestinal barriers. mBio 9(3), e00915-18. Details PubMed Open Access
(2018) Adjunctive interferon-γ immunotherapy in a pediatric case of Aspergillus terreus infection. Eur J Clin Microbiol Infect Dis [Accepted] Details PubMed
(2018) Bis-guanylhydrazones as efficient anti-Candida compounds through DNA interaction. Appl Microbiol Biotechnol 102(4), 1889-1901. Details PubMed
(2018) Processing of Candida albicans Ece1p is critical for Candidalysin maturation and fungal virulence. MBio 9(1), pii: e02178-17. Details PubMed Open Access
(2017) Candidalysin drives epithelial signaling, neutrophil recruitment, and immunopathology at the vaginal mucosa. Infect Immun , pii: IAI.00645-17. Details PubMed
(2016) Candidalysin is a fungal peptide toxin critical for mucosal infection. Nature 532(7597), 64-68. Details PubMed Open Access
(2016) The missing link between Candida albicans hyphal morphogenesis and host cell damage. PLOS Pathog 12(10), e1005867. (Review) Details PubMed
(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. Details PubMed
(2014) Distinct roles of Candida albicans-specific genes in host-pathogen interactions. Eukaryot Cell 13(8), 977-989. Details PubMed
(2011) The Candida albicans-specific gene EED1 encodes a key regulator of hyphal extension. PLOS One 6(4), e18394. Details PubMed
(2011) Host-pathogen interactions and virulence-associated genes during Candida albicans oral infections. Int J Med Microbiol 301(5), 417-422. (Review) Details PubMed
(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. Details PubMed Open Access