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