Fungi as Part of the Microbiota and Interactions with Intestinal Bacteria.

The human microbiota consists of bacteria, archaea, viruses, and fungi that build a highly complex network of interactions between each other and the host. While there are many examples for commensal bacterial influence on host health and immune modulation, little is known about the role of commensal fungi inside the gut community. Up until now, fungal research was concentrating on opportunistic diseases caused by fungal species, leaving the possible role of fungi as part of the microbiota largely unclear. Interestingly, fungal and bacterial abundance in the gut appear to be negatively correlated and disruption of the bacterial microbiota is a prerequisite for fungal overgrowth. The mechanisms behind bacterial colonization resistance are likely diverse, including direct antagonism as well as bacterial stimulation of host defense mechanisms. In this work, we will review the current knowledge of the development of the intestinal bacterial and fungal community, the influence of the microbiota on human health and disease, and the role of the opportunistic yeast C. albicans. We will furthermore discuss the possible benefits of commensal fungal colonization. Finally, we will summarize the recent findings on bacterial-fungal interactions.

Rapid proliferation due to better metabolic adaptation results in full virulence of a filament-deficient Candida albicans strain.

The ability of the fungal pathogen Candida albicans to undergo a yeast-to-hypha transition is believed to be a key virulence factor, as filaments mediate tissue damage. Here, we show that virulence is not necessarily reduced in filament-deficient strains, and the results depend on the infection model used. We generate a filament-deficient strain by deletion or repression of EED1 (known to be required for maintenance of hyphal growth). Consistent with previous studies, the strain is attenuated in damaging epithelial cells and macrophages in vitro and in a mouse model of intraperitoneal infection. However, in a mouse model of systemic infection, the strain is as virulent as the wild type when mice are challenged with intermediate infectious doses, and even more virulent when using low infectious doses. Retained virulence is associated with rapid yeast proliferation, likely the result of metabolic adaptation and improved fitness, leading to high organ fungal loads. Analyses of cytokine responses in vitro and in vivo, as well as systemic infections in immunosuppressed mice, suggest that differences in immunopathology contribute to some extent to retained virulence of the filament-deficient mutant. Our findings challenge the long-standing hypothesis that hyphae are essential for pathogenesis of systemic candidiasis by C. albicans.