The impact of spore surface attributes of Lichtheimia corymbifera during infection of human cells.

Dolly Montano1,2, Volker U. Schwartze1,2, Mohamed Hassan1,2, Kerstin Voigt1,2
[1] Friedrich-Schiller University, Faculty of Biological Sciences, Institute of Microbiology. Jena, Germany. 
[2] Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute. Jena, Germany.

Objectives: Lichtheimia corymbifera is a causative agent of mucormycosis, a life-threatening infection caused by members of the fungal order Mucorales. Mucormycosis infection is associated with a high mortality due to its rapid destruction of tissue, difficult early-diagnosis, and resistance to various antifungal agents, which reduces therapeutic options. A previous study reported the full genome sequences of L. corymbifera, providing a molecular basis to understand its pathogenicity-associated features. Moreover, studies in our group predict genes encoding proteins involved in host-pathogen interactions. Spore cell-wall proteins and pigments are known to play an important role in other fungal pathogens like A. fumigatus when interacting with the host. However, little is known about the contribution of spore surface proteins and pigments of L. corymbifera when initiating the infection of host cells. Therefore, we will study the role of candidate spore surface proteins and pigments in adhesion, invasion, and damage to endothelial, epithelial, and alveolar macrophage cells, which represent the first line of defense during pulmonary infections.

Methods:  To determine the most relevant players during the initiation of infection, we plan to use in vitro infection models, confocal laser scanning microscopy and flow cytometric analysis. In addition, we will employ a yeast surface display and generate specific antibodies that will mask the candidate surface proteins. In a final step, we will confirm the role of these proteins by silencing the genes involved in initial host-pathogen interactions.

Results: With all these strategies, we expect to determinate mechanisms developed by L. corymbifera that challenge pulmonary epithelial and endothelial cells, the primary custodians of the lung. Furthermore, we will uncover specific ligand-receptor interactions involved in the invasion of the host cells, as well as, strategies established by this pathogen to avoid the host immune response and survive inside the cells, such as in macrophages. 

Conclusion: As a long-term, our findings will provide new insights to develop novel diagnostics and treatments to counteract infections caused by L. corymbifera.

The impact of spore surface attributes of Lichtheimia corymbifera during infection to human cells