Candida albicans promotes TSST-1 production by Staphylococcus aureus through glucose depletion and relief of CcpA-mediated repression

ABSTRACT Menstrual toxic shock syndrome (mTSS) is a rare yet life-threatening disease that is caused when the opportunistic pathogenic bacterium Staphylococcus aureus releases the toxic shock syndrome toxin 1 (TSST-1) superantigen, which triggers systemic inflammation. The main risk factor for mTSS is prolonged use of intravaginal products, which facilitates S. aureus growth and TSST-1 production in menstrual blood. However, some studies suggest that the vaginal microbiota may also play a role in mTSS occurrence. A previous study reported that the presence of S. aureus in menstrual fluids was correlated with the simultaneous presence of Candida species, particularly C. albicans . Here, we assessed the potential involvement of C. albicans in the stimulation of TSST-1 production by incubating S. aureus strains with C. albicans culture supernatants and measuring TSST-1 production. We found that the growth of C. albicans depleted the available glucose, thereby alleviating the CcpA-mediated repression of the tst gene, which encodes TSST-1, and enabling activation of its expression by SaeRS activity. These results highlight the importance of vaginal microbiota and nutrient availability with regard to the regulation of S. aureus virulence in the context of mTSS. IMPORTANCE Menstrual toxic shock syndrome (mTSS) is a life-threatening disease caused by toxic shock syndrome toxin 1 (TSST-1)-producing strains of Staphylococcus aureus . While tampons are a known risk factor, the vaginal microbiota may also increase mTSS risk. Our findings reveal that the yeast Candida albicans , a frequent colonizer of the vaginal mucosa, stimulates TSST-1 production of S. aureus by depleting glucose, a key regulator of tst gene expression. This study highlights how C. albicans , which is part of the vaginal microbiota, can amplify S. aureus virulence through metabolic interactions. These findings may also carry clinical implications by identifying vaginal colonization with C. albicans as a potential biomarker for heightened mTSS susceptibility, specifically in individuals harboring TSST-1-producing strains of S. aureus .