Candida albicans and Staphylococcus aureus reciprocally promote their virulence factor secretion and pro-inflammatory effects

We showed that co-culturing of <i>C. albicans</i> and <i>S. aureus</i> promoted the secretion of 7 cytolytic, 11 proteolytic, and 3 lipolytic extracellular virulence factors (ECVFs) and impacted non-ECVFs, owing to Als1/Als3-mediated interactions, the presence of <i>C. albicans</i>, or its pH maintenance. Co-culturing promotes <i>C. albicans</i> hypha formation and β-glucan masking, suggesting that co-culturing enhances both <i>C. albicans</i> invasion and immune evasion. Moreover, the secretome of <i>C. albicans-S. aureus</i> co-culture increased pro-inflammatory pathways including promoting TNF-, NFKB-, and Toll-like receptor signaling pathways, as well as cytokine-cytokine receptor interactions in macrophages. Our findings support that <i>C. albicans</i> and <i>S. aureus</i> reciprocally promote their virulence potential and pro-inflammatory effects, which may provide mechanistic insights into the increased morbidity and mortality during their co-infection <i>in vivo</i>.