The opportunistic human fungal pathogen Candida albicans promotes the growth and proliferation of commensal Escherichia coli through an iron-responsive pathway.

Candida albicans is a commensal fungal species that commonly colonizes a heterogeneous mixture of human body where it intimately interacts with other microbes in the host environment such as the gastrointestinal (GI) tract. Most studies in fungal-bacterial interactions are about synergistic or antagonistic effects of bacterial functions on fungal physiological activities including pathogenicity. Very few studies have been demonstrated about the role of fungi on bacteria. In this study, we investigated the interactions between C. albicans and the bacterium Escherichia coli and unexpectedly observed that C. albicans enhances growth and proliferation of Escherichia coli strain K12 by facilitating its cell division. Importantly, we found, based on our genetic screens, that both fungus- and bacterium-derived factors, including the iron-responsive transcription factors Sef1 and Sfu1 in C. albicans and the siderophere enterobactin transporters FepD and FepG in E. coli, actively contribute to this transkingdom interaction. Deletion of SFU1 or SEF1 caused a dramatic reduction in growth enhancement of E. coli. Compared to the wild type E. coli, the enhanced growth of both fepD and fepG null mutants were largely dampened. However, the E. coli mutant lacking entB, a key enzyme catalyzing the biosynthesis of siderophore enterobactin, showed similar growth enhancement as the wild type when co-inoculated with C. albicans. C. albicans promotes growth and proliferation of the commensal bacterium E. coli and an iron-responsive signaling pathway appears to be required. C. albicans may act to supply a siderophere-like molecule that captures the environmental iron to promote the growth of E. coli. Our studies gave insight into a novel interacting mechanism operative in interspecies communication that occurs when bacteria and fungi co-exist.