Host-pathogen interactions: Candida albicans infection in the planarian flatworm Schmidtea mediterranea

Candida albicans is one of the most prominent human fungal pathogens. The usage of vertebrate and invertebrate in vivo models of candidiasis have provided important insights into the pathogenesis of fungal pathogens. However, there are still limitations with the available animal models used to analyze the early stages of fungal infection and the ensuing response in both the host and the pathogen. Here, I describe the development and characterization of a new model that improves the ability to study the initial stages of a fungal infection. Specifically, I studied early infection stages of C. albicans infection using the planarian flatworm, Schmidtea mediterranea. I demonstrated that C. albicans successfully infects and colonizes planarian tissue. The virulence of C. albicans in the planarian model is dependent on the ability of C. albicans to adhere to and to form filaments during infection, which is similar to what has been observed in vertebrate infection models. Interestingly, however, I show that adherence of C. albicans to the planarian epithelial layer leads to a unique multi-system response (not shown using other models) involving the nervous and excretory systems along with transcriptomic changes resembling the early wound response. I propose that the increased activity of the host excretory system may be mediated by cholinergic neurons to increase mucus secretion leading to a reduction in C. albicans adhesion. Mechanistically, I identified that C. albicans infection triggers increased expression of the Dectin signaling pathway and stem cell hyperproliferation. Collectively, I demonstrate that planarians are a tractable model system to investigate host-pathogen interactions resembling the virulence and characteristics of an early mucosal fungal infection in mammals. In addition, my work demonstrates that planarians are useful in understanding unique aspects of how fungal pathogens interact with their hosts that are not currently observable using other animal model systems