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.
|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|
|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|