Candida albicans and Enterococcus faecalis in the gut: synergy in commensalism?

Abstract

The fungus Candida albicans and the gram-positive bacterium Enterococcus faecalis are both normal residents of the human gut microbiome and cause opportunistic disseminated infections in immunocompromised individuals. Using a nematode infection model, we recently showed that co-infection resulted in less pathology and less mortality than infection with either species alone and this was partly explained by an interkingdom signaling event in which a bacterial-derived product inhibits hyphal morphogenesis of C. albicans. In this addendum we discuss these findings in the contest of other described bacterial-fungal interactions and recent data suggesting a potentially synergistic relationship between these two species in the mouse gut as well. We suggest that E. faecalis and C. albicans promote a mutually beneficial association with the host, in effect choosing a commensal lifestyle over a pathogenic one.

Keywords: C. elegans; Candida; Enterococcus; hyphal morphogenesis; microbiome.

Figure 1. A C. elegans infection model reveals attenuation of virulence in C. albicans-E. faecalis coinfections. (A-D) Fluorescence imaging shows the two species mixing in the worm and the absence of hyphal growth in the coinfection. Worms were infected with yCherry labeled-C. albicans alone (A and B) or coinfected with GFP-labeled E. faecalis (C and D) and imaged using DIC (A and C) or fluorescence (B and D). Panels (E-H) Ultrastructural analysis of nematode physiology. Worms were infected with C. albicans alone (E and F) or with both species (G and H) before processing for transmission electron microscopy. The disruption of the normal gut physiology in the C. albicans-infected worms relative to the coinfection is apparent. The scale bar in panel F is 1 µm and applied to (E-H).

Figure 2. A speculative model for Candida-Enterococcus interactions in the gut. In the worm gut, C. albicans transitions from a commensal mode characterized by yeast-form growth to an invasive, hyphal and pathogenic state. This transition is inhibited by the presence of E. faecalis through molecule(s) secreted in an FsrB-dependent manner, thus maintaining the commensal association with the host. Likewise, mono-infection with E. faecalis imposes significant gut pathology, which is reduced in the presence of C. albicans through an unknown mechanism. In the mammalian gut, the work from Hufnagel and colleagues suggests that these two species also promote a commensal association with the host which we speculate can be disrupted by changes to microbe or host factors leading to infection. C. albicans cells are shown in blue, E. faecalis in red, and gut epithelial cells in orange.