Project A6

Surface proteins of Lichtheimia corymbifera as virulence determinants

Like Aspergillus fumigatus, Lichtheimia corymbifera is a ubiquitous saprophyte which can cause life-threatening infections, mainly in immunocompromised patients. While these infections (mucormycoses) are uncommon infections, they have been increasingly recognized during the last decades and are associated with high mortality rates. However, only little is known about the pathogenicity mechanisms of these fungi and therapeutic options are still limited.

The cell wall represents the outer border of fungal cells and is crucial for the stability of fungal cells under changing environmental conditions. In fungal pathogens the cell wall also plays a crucial role during the interaction with the host. The main part of the cell wall is composed of carbohydrates such as glucan, chitin and chitosan, which define the interaction with host immune cells. A variety of cell wall located proteins have also been identified in fungi, including adhesins, invasins and hydrolytic enzymes. Such surface proteins are known to contribute to the virulence of fungal pathogens and represent, due to their accessible location, interesting targets for the development of antifungal therapeutics.

In project A6, we aim to get a better understanding of the surface proteins of L. corymbifera and how they are involved in the interaction with the host. Previously, we sequenced and analyzed the genome of L. corymbifera and identified putative target proteins. Using proteomic approaches, we verified the location of several proteins on spore surfaces and identified interesting candidates such as the hydrophobic binding protein HsbA. Since the infection process also involves the hyphal stages of the fungus, stage-specific surface proteomic studies will be conducted. Based on these data we will select target proteins for in-depth molecular and immune biological studies and elucidate their role in the interaction with different host cells.

Macrophage with attached spore of Lichtheimia. Photo: Schrade, Charité Berlin.
Macrophage with attached spore of Lichtheimia. Photo: Schrade, Charité Berlin.
Principal Investigator
Author Year Title Journal Links
Jia LJ, Rafiq M, Radosa L, Hortschansky P, Cunha C, Cseresnyés Z, Krüger T, Schmidt F, Heinekamp T, Straßburger M, Löffler B, Doenst T, Lacerda JF, Campos A, Figge MT, Carvalho A, Kniemeyer O, Brakhage AA 2023 Aspergillus fumigatus hijacks human p11 to redirect fungal-containing phagosomes to non-degradative pathway. Cell Host & Microbe: 31,3 Cell Host & Microbe
Garloff V, Krüger T, Brakhage A, Rubio I. 2023 Control of TurboID-dependent biotinylation intensity in proximity ligation screens. J Proteomics. J Proteomics 15;279:104886 PubMed
Mirhakkak MH, Chen X, Ni Y, Heinekamp T, Sae-Ong T, Xu LL, Kurzai O, Barber AE, Brakhage AA, Boutin S, Schäuble S, Panagiotou G 2023 Genome-scale metabolic modeling of Aspergillus fumigatus strains reveals growth dependencies on the lung microbiome. Nat Commun. 14(1):4369 PubMed
Möckel L, Meusemann K, Misof B, Schwartze VU, De Fine Licht HH, Voigt K, Stielow B, de Hoog S, Beutel RG, Buellesbach J 2022 Phylogenetic revision and patterns of host specificity in the fungal subphylum entomophthoromycotina. Microorganisms 10: 256 PubMed
Acosta-España JD, Voigt K 2022 Mini Review: Risk Assessment, Clinical Manifestation, Prediction, and Prognosis of Mucormycosis: Implications for Pathogen- and Human-Derived Biomarkers. Frontiers in Microbiology 895989 Front. Microbiol.
Acosta España JD, Hassan MA, Hea-Reung P,  Schwartze VU, Schäuble S,  Krüger T,  Kniemeyer O, Brakhage AA, Voigt K 2022 Novel hydrophobic binding surface proteins are instrumental for phagocytosis of Lichtheimia corymbifera by macrophages. Medical Mycology 60 (1) :myac072P343 Medical Mycology
Böttcher B, Driesch D, Krüger T, Garbe E, Gerwien F, Kniemeyer O, Brakhage AA, Vylkova S 2022 Impaired amino acid uptake leads to global metabolic imbalance of Candida albicans biofilms. NPJ Biofilms Microbiomes. 8(1): 78 PubMed
Montaño DE, Hartung S, Wich M, Ali R, Jungnickel B, von Lilienfeld-Toal M, Voigt K 2022 The TLR-NF-kB axis contributes to the monocytic inflammatory response against a virulent strain of Lichtheimia corymbifera, a causative agent of invasive mucormycosis. Front Immunol. 13: 882921 PubMed
Acosta-España JD, Voigt K 2022 An old confusion: Entomophthoromycosis versus mucormycosis and their main differences. Front Microbiol. 13: 1035100. PubMed
Hassan MIA, Keller M, Hillger M, Binder U, Reuter S, Herold K, Telagathoti A, Dahse HM, Wicht S, Trinks N, Nietzsche S, Deckert-Gaudig T, Deckert V, Mrowka R, Terpitz U, Saluz HP, Voigt K 2021 The impact of episporic modification of Lichtheimia corymbifera on virulence and interaction with phagocytes. Comput Struct Biotechnol J 19: 880-896 PubMed
Yu Y, Wolf AK, Thusek S, Heinekamp T, Bromley M, Krappmann S, Terpitz U, Voigt K, Brakhage AA, Beilhack A 2021 Direct visualization of fungal burden in filamentous fungus-infected silkworms. J Fungi (Basel) 7: 136 PubMed
Stanford FA, Matthies N, Cseresnyés Z, Figge MT, Hassan MIA, Voigt K 2021 Expression patterns in reductive iron assimilation and functional consequences during phagocytosis of Lichtheimia corymbifera, an emerging cause of Mucormycosis. J Fungi (Basel) 7: 272 PubMed
Voigt K, James TY, Kirk PM, Santiago ALCMA, Waldman B, Griffith GW, Fu M, Radek R, Strassert JFH, Wurzbacher C, Jerônimo GH, Simmons DR, Seto K, Gentekaki E, Hurdeal VG, Hyde KD, Nguyen TTT, Lee HB 2021 Early-diverging fungal phyla: taxonomy, species concept, ecology, distribution, anthropogenic impact, and novel phylogenetic proposals. Fungal Divers 1-40 (Review) [Epub ahead of print] PubMed
Hassan MIA, Kruse J, Krüger T, Dahse HM, Cseresnyés Z, Blango MG, Slevogt H, Hörhold F, Ast V, König R, Figge MT, Kniemeyer O, Brakhage AA, Voigt K 2020 Functional surface proteomic profiling reveals the host heat-shock protein A8 as a mediator of Lichtheimia corymbifera recognition by murine alveolar macrophages. Environ Microbiol 22: 3722-40 PubMed
Cseresnyés Z, Hassan MA, Dahse HD, Voigt K, Figge MT 2020 Quantitative impact of cell membrane fluorescence labeling on phagocytosis measurements in confrontation assays. Front Microbiol 11: 1193 PubMed
Montaño DE, Voigt K 2020 Host immune defense upon fungal infections with mucorales: Pathogen-immune cell interactions as drivers of inflammatory responses. J Fungi (Basel) 6: E173 (Review) PubMed
Stanford FA, Voigt K 2020 Iron assimilation during emerging infections caused by opportunistic fungi with emphasis on mucorales and the development of antifungal resistance. Genes (Basel) 11: E1296 (Review) PubMed
Hassan MIA, Cseresnyés Z, Al-Zaben N, Dahse HM, de Oliveira RJV, Walther G, Voigt K, Figge MT 2019 The geographical region of origin determines the phagocytic vulnerability of Lichtheimia strains. Environ Microbiol 21: 4563-81 PubMed
Hassan MIA, Voigt K 2019 Pathogenicity patterns of mucormycosis: epidemiology, interaction with immune cells and virulence factors. Med Mycol 57: S245-S256 PubMed
Gryganskyi AP, Golan J, Dolatabadi S, Mondo S, Robb S, Idnurm A, Muszewska A, Steczkiewicz K, Masonjones S, Liao HL, Gajdeczka MT, Anike F, Vuek A, Anishchenko IM, Voigt K, de Hoog GS, Smith ME, Heitman J, Vilgalys R, Stajich JE 2018 Phylogenetic and phylogenomic definition of Rhizopus species. G3 (Bethesda) 8: 2007-18 PubMed
Sieber P, Voigt K, Kämmer P, Brunke S, Schuster S, Linde L 2018 Comparative study on alternative splicing in human fungal pathogens suggests its involvement during host invasion. Front Microbiol 9: 2313 Front Microbiol
Arnesen JA, Malagocka J, Gryganskyi A, Grigoriev IV, Voigt K, Stajich JE, De Fine Licht HH 2018 Early diverging insect-pathogenic fungi of the order Entomophthorales possess diverse and unique subtilisin-like serine proteases. G3 (Bethesda) 8: 3311-19 PubMed
Schulze B, Rambach G, Schwartze VU, Voigt K, Schubert K, Speth C, Jacobsen ID 2017 Ketoacidosis alone does not predispose to mucormycosis by Lichtheimia in a murine pulmonary infection model. Virulence 8: 1657-67 PubMed