Zebrafish embryos as a unique model host organism to study in vivo Candida albicans biofilm development.

Candida albicans is a commensal organism in most humans. The possible beneficial function for the host is unknown. Under some conditions, such as a weakened immune system, this organism can become a deadly pathogen. For this it has a large array of virulence factors, such as morphogenesis and the production of different types of hydrolyses. Another important virulence factor is biofilm formation. Biofilms are three-dimentional structures consisting of different morphological forms of C. albicans cells (yeast, hyphae and pseudohyphae) surrounded by a complex extracellular matrix. They can form on mucosal tissue but also on any implant material that is inserted into patients. This matrix protects cells inside a biofilm from the host immune system as well as from antifungal drugs. Several research groups have investigated biofilm development, mainly in vitro, but also in vivo in rodent model systems. The main problem is that only a few time points (12hrs, 24hrs) were investigated. Different stages can be identified but the exact moments of differentiation are not known. In this project we will use zebrafish larvae to study biofilm formation as these larvae are transparent, allowing continuous imaging of what is going on during biofilm formation. We will develop a device-related infection by also injecting polystyrene microspheres, a substrate to which C. albicans cells bind. This project will allow us to visualize biofilm formation in real time for the first time.