C. albicans and S. aureus 1+1=3

During immune deficiency, the highly invasive, but modestly virulent fungus Candida albicans and the non-invasive, but highly virulent bacterium Staphylococcus aureus can induce both highly invasive and highly virulent (lethal) infections when together. Previous studies have shown that this increase can be attributed to 1) the co-invasion of S. aureus with invading C. albicans hypha and 2) the systemic dissemination of the bacterium, which is aided by oral immune cells. The mechanisms that drive the co-invasion and immune aided dissemination of S. aureus, however, remain unknown. In this thesis we first describe how the human oral bacteriome and mycobiome develop and how S. aureus and C. albicans can integrate into the oral microbiome. Next, we review the various aspects of the human oral immune system that prevent C. albicans and S. aureus virulence and describe how various immune deficiencies can allow for increased virulence in immunocompromised individuals. The following chapters describe how we developed a novel in vitro model system to study the effect of co-culturing on C. albicans/S. aureus growth and (co-)invasion. The following chapter describes how we studied the effect of co-culturing on secreted virulence factors and their cytotoxic potential towards human oral cells. Finally, we describe how we studied the effects of the C. albicans, S. aureus, and co-culture secretome on human macrophages. Our studies showed that co-culturing promoted all tested virulence traits of C. albicans and S. aureus beyond that of the virulence of both monocultures added together.