Cross-kingdom quorum sensing: mechanisms driving Candida albicans and Staphylococcus aureus synergistic pathogenesis

Background Co-infection with Staphylococcus aureus and Candida albicans represents a prevalent, clinically important polymicrobial challenge that can be associated with worse outcomes than monomicrobial infection. Emerging evidence indicates that their synergistic pathogenicity is shaped by quorum sensing (QS) related and other cross-kingdom interactions.Objective To summarize current evidence on cross-kingdom interactions involving the S. aureus agr quorum-sensing system and the C. albicans farnesol signalling pathway and their contributions to polymicrobial pathogenicity.Design This narrative review synthesizes current evidence on QS-related, metabolic, environmental, structural, and host-mediated mechanisms underlying S. aureus - C. albicans interactions.Results Extracellular pH regulation, ribose metabolism, mixed-biofilm architecture, and farnesol-induced stress adaptation modulate bacterial virulence and antimicrobial tolerance. Furthermore, microbial signalling and host innate immune responses interact bidirectionally to shape infection outcomes. Importantly, direct recognition of a C. albicans-derived quorum-sensing molecule by a defined S. aureus QS receptor has not yet been demonstrated.Conclusions QS-targeted and anti-adhesion/anti-virulence strategies may offer therapeutic opportunities, but their efficacy requires further validation in host-relevant oral and systemic infection models.