Candida albicans Enables Staphylococcus aureus “Hitchhiking” Across Mucosa Original paper

What was studied?

This study investigated a novel mechanism by which Candida albicans facilitates the invasion and systemic dissemination of Staphylococcus aureus through mucosal tissue. Specifically, the concept of Candida albicans Staphylococcus aureus ‘hitchhiking’ was examined, where researchers explored whether S. aureus can adhere to the invasive hyphal form of C. albicans via specific adhesin interactions, enabling it to bypass the need for a traditional epithelial breach. Key attention was given to the role of the C. albicans Als3p adhesin in mediating this “microbial hitchhiking,” allowing S. aureus to bind to fungal hyphae, penetrate tissue, and cause systemic disease. This hypothesis was tested through in vitro biofilm assays, ex vivo tongue models, and a murine model of oral co-colonization.

Who was studied?

The study used in vitro dual-species biofilm models, ex vivo murine tongue tissue, and immunosuppressed C57BL/6J mice. Multiple strains of S. aureus, including USA300 JE2 wild-type and 25 adhesin-deficient mutants, were tested for their binding ability to C. albicans hyphae. The fungal strains included C. albicans SC5314 wild-type, an Als3p-deficient mutant (als3Δ/Δ), and an Als3p-complemented strain. These models enabled evaluation of microbial binding, tissue invasion, and systemic dissemination under conditions mimicking human mucosal colonization in immunocompromised hosts.

Most important findings

The researchers found that S. aureus specifically binds to the hyphal form of C. albicans via the fungal Als3p adhesin. This interaction is essential for bacterial invasion across the mucosal barrier and subsequent dissemination. In vitro and real-time microscopy confirmed that S. aureus rapidly attaches to C. albicans hyphae. In the murine model, systemic infection and mortality occurred only when mice were co-colonized with S. aureus and Als3p-expressing C. albicans. Mice co-infected with the Als3p-deficient mutant showed no dissemination or mortality. Recovery of S. aureus and C. albicans from kidney tissue was only observed in mice infected with strains expressing Als3p. Additionally, three S. aureus adhesin mutants (ΔfnbB, ΔsasF, Δatl) showed significantly reduced hyphal binding, but no single staphylococcal adhesin was solely responsible, implying redundancy in adhesin interactions.

Key implications

This study introduces a paradigm-shifting concept in microbial pathogenesis: fungal-mediated bacterial invasion through mucosal surfaces. The discovery that C. albicans hyphae can serve as conduits for systemic S. aureus infection has profound clinical implications, particularly in immunocompromised patients where these microbes frequently co-colonize mucosal surfaces. This work identifies Als3p as a critical target for disrupting this pathogenic synergy, suggesting that Als3p or C. albicans inhibition may serve as a preventive strategy against invasive staphylococcal infections. The findings also underscore the need to screen for C. albicans colonization in critically ill patients as a risk factor for secondary bacterial sepsis.