Fungal Infections

Hans de Cock

 

Fungi have developed strategies to live and survive on and in human hosts. The host-immune system is involved in clearing fungi thereby preventing the development of a mycosis. Candida spp, Cryptococcus spp and Aspergillus spp belong to the most life threatening fungal species for humans. Furthermore, fungi live on hosts and the skin is harbouring Malassezia spp which are regarded commensals as well as opportunistic pathogens. Malassezia spp have been associated with different dermatologic conditions of high prevalence including dandruff, seborrheic dermatitis and pityriasis versicolor, among others. Moreover, they have been related to blood infections in neonates, IBD and pancreatic cancer. In my lab we focus on Malassezia spp and Aspergillus spp.

 

Malassezia project

Malassezia spp are characterized by lipid dependency, due to the lack of a cytosolic FAS which results in a defect to synthesis of fatty acids. Consequently, they are dependent on lipids on the skin for growth. The skin functions in the innate defence against pathogens due to its low water content, acidic pH, its microbiota, and antimicrobial compounds like antimicrobial peptides and free fatty acids. Understanding lipid dependency of Malassezia will help to understand how these yeasts establish themselves as part of the skin microbiota, which adaptation mechanisms are involved, and how a shift to pathogenicity can occur. In this project we collaborate with Dr. Adriana Celis, Universidad de Los Andes, Faculty of Science, Bogota, Colombia.

 

A. fumigatus project

Daily we come into contact with Aspergillus fumigatus, mostly by inhalation of spores without being affected. A. fumigatus infections are especially developing in humans with a weakened immune system or with certain lung diseases like cystic fibrosis (CF).  Due to the increased use of immunosuppressive drugs the number of fungal infections is increasing in the western world. Furthermore, increased resistance to antifungals like azoles compromises patient treatment.

We study the molecular details of interactions between A. fumigatus and lung epithelial cells in different model systems encompassing both submerged culturing of lung cells as well as air-liquid organoid models. We investigating how new antimicrobial compounds (e.g. peptides) affect fungal growth and development in these lung-model systems. We aim to develop new antifungal agents to prevent infections with A. fumigatus. Furthermore, we investigate how A. fumigatus adapts to the host during chronic infections in CF patients. In this NCOH project we collaborate with various partners at the UU campus (UMCU, WKZ, Veterinairy Sciences) as well as Nijmegen (CWH).