Pathogenicity mechanisms of Candida albicans and Malassezia

pathogenizity

Genetic diversity in C. albican

The immune system plays an active role in maintaining a stable equilibrium between commensal fungi and the host to prevent fungal overgrowth and disease. In addition to host factors, the genetic diversity in the fungal species contribute additional risk factors in susceptible hosts. C. albicans displays an intrinsically high diversity in its population genetic structure.The genetic variations that exist within the fungal species result in functional differences between individual strains, and this natural diversity of C. albicans modulates the outcome of the interaction between the fungus and the host in mucosal tissues. By using genome-wide approaches this project aims at identifying fungal genetic factors associated with the variability in the outcomes of fungal-host interactions. This shall lead to a better understanding of the impact of C. albicans genetic diversity on its pathogenesis. Moreover, we are interested to understand how the host environment drives microevolution of C. albicans, which in turn may contribute to diversification of the fungal species. For this project we closely collaborate with the labs of Christophe d’Enfert (Institut Pasteur) and Dominique Sanglard (University of Lausanne).

Virulence factors of Malassezia

Little is known so far about the genetic diversity of Malassezia, although inter- and intraspecies variations in the fungal genus likely affect the interaction of the skin commensal yeast with the host, similarly to what is known for C. albicans. It also remains unclear whether certain species of Malassezia are more pathogenic than others and associated with specific skin diseases. In this project, we examine the functional relevance of putative virulence factors of Malassezia using engineered mutant strains and clinical fungal isolates from atopic dermatitis patient cohorts, respectively. For this project we have established close collaborations with the labs of Joseph Heitman (Duke University) and Tom Dawson (A*STAR Singapore) as well as the University Hospital Zürich.

Together, this works aims at identifying novel fungal virulence factors that determine the balance between commensalism and disease.

Funding:             

Swiss National Science Foundation – Sinergia program  http://p3.snf.ch/project-173863

Marie Curie Actions – Innovative Training Network https://www.funhomic.eu/en

Funding: Swiss National Science Foundation http://p3.snf.ch/project-189255

LEGEND: Different isolates of C. albicans differ greatly in their functional characteristics such as the degree of filamentation (left) and the capacity to damage epithelial cells (right), both of which represent important determinants of pathogenicity.