Escherichia coli, but Not Staphylococcus aureus, Functions as a Chelating Agent That Exhibits Antifungal Activity against the Pathogenic Yeast Candida albicans

Abstract

Humans are colonized by diverse populations of microbes. Infections by Candida albicans, an opportunistic fungal pathogen, are a result of imbalances in the gut microbial ecosystem and are due to the suppressed immunity of the host. Here, we explored the potential effects of the polymicrobial interactions of C. albicans with Staphylococcus aureus, a Gram-positive bacterium, and Escherichia coli, a Gram-negative bacterium, in dual and triple in vitro culture systems on their respective growth, morphology, and biofilms. We found that S. aureus promoted the fungal growth and hyphal transition of C. albicans through cell-to-cell contacts; contrarily, both the cell and cell-free culture filtrate of E. coli inhibited fungal growth. A yet to be identified secretory metabolite of E. coli functionally mimicked EDTA and EGTA to exhibit antifungal activity. These findings suggested that E. coli, but not S. aureus, functions as a chelating agent and that E. coli plays a dominant role in regulating excessive growth and, potentially, the commensalism of C. albicans. Using animal models of systemic candidiasis, we found that the E. coli cell-free filtrate suppressed the virulence of C. albicans. In general, this study unraveled a significant antimicrobial activity and a potential role in the nutritional immunity of E. coli, and further determining the underlying processes behind the E. coli–C. albicans interaction could provide critical information in understanding the pathogenicity of C. albicans.