| Summary: | <i>Candida albicans</i> is a pathobiont of the gastrointestinal tract. It can contribute to the diversity of the gut microbiome without causing harmful effects. When the immune system is compromised, <i>C. albicans</i> can damage intestinal cells and cause invasive disease. We hypothesize that a therapeutic approach against <i>C. albicans</i> infections can rely on the antimicrobial properties of probiotic bacteria. We investigated the impact of the probiotic strain <i>Escherichia coli</i> Nissle 1917 (EcN) on <i>C. albicans</i> growth and its ability to cause damage to intestinal cells. In co-culture kinetic assays, <i>C. albicans</i> abundance gradually decreased over time compared with <i>C. albicans</i> abundance in the absence of EcN. Quantification of <i>C. albicans</i> survival suggests that EcN exerts a fungicidal activity. Cell-free supernatants (CFS) collected from <i>C. albicans</i>-EcN co-culture mildly altered <i>C. albicans</i> growth, suggesting the involvement of an EcN-released compound. Using a model of co-culture in the presence of human intestinal epithelial cells, we further show that EcN prevents <i>C. albicans</i> from damaging enterocytes both distantly and through direct contact. Consistently, both <i>C. albicans</i>’s filamentous growth and microcolony formation were altered by EcN. Taken together, our study proposes that probiotic-strain EcN can be exploited for future therapeutic approaches against <i>C. albicans</i> infections.
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