Professor Janet Quinn (Newcastle University) and Professor Lars Erwig and Dr Donna MacCallum (University of Aberdeen)
PhD Student: Dr Beatrice Achan
Start date: 01 February 2014
Project Title:The Role of Candida albicans oxidative stress responses in triggering filamentation and macrophage escape following phagocytosis.
Candida albicans is an important pathogen of humans causing approximately 400,000 life-threatening infections each year. We defend ourselves from C.albicans by immune defence mechanisms. This includes the production of toxic oxidising chemicals such as hydrogen peroxide (H202), by specialised cells such as macrophages. However, C.albicans is very adept at surviving exposure to H202. Once this fungus is engulfed by a macrophage, it produces enzymes to detoxify H202 and it switches to a filamentous growth mode. Such filaments stretch and pierce the macrophage cell membrane, thus killing the macrophage and facilitating escape of the fungal pathogen. However, little is known about the mechanisms underlying the filamentation of C. albicans within macrophages. We have recently found that exposure of C. albicans to H202 triggers filamentation, and that the ability of this pathogen to mount robust defences against H202 is essential for filamentation inside the macrophage. In this propsal we build on these significant findings and combine the international expertise of two UK centres, studying fungal responses to H202 ( Newcastle) and the ability of fungal cells to evade immune defences and cause disease (Aberdeen), to understand how C.albicans responses to oxidising chemicals allow this pathogen to evade host defences.