Escape of Staphylococcus aureus from Host Phagocytic Cells Mediated by the Candida albicans Invasive Hyphae

Objectives: The fungal and bacterial species, Candida albicans and Staphylococcus aureus, respectively, are important microbial pathogens that are often co-isolated from the host. As a dimorphic fungal pathogen, C. albicans is capable of switching morphology between yeast and a filamentous hyphal form. Unlike S. aureus, the invasive hyphae allow C. albicans to escape and evade killing by host phagocytic cells such as macrophages. In this study, we designed assays to validate the hypothesis that the ability of C. albicans to escape from macrophages provides co-phagocytosed S. aureus cells with the means to escape phagocytic killing.
Methods: To demonstrate the importance of the C. albicans hyphae in the process, we used a genetically modified C. albicans strain where hyphae production can be controlled. Using a mouse macrophage cell line, S. aureus and C. albicans cells were added and phagocytosis was allowed to occur over time. Macrophage lysis and killing by the invading hyphae was assessed using a macrophage viability stain and the release of S. aureus cells from macrophages was quantified by growth on bacterial media. To visualize the co-escape process, scanning electron microscopy and time-lapse fluorescent confocal laser scanning microscopy using a cocktail of fluorescent dyes were performed.
Results: Findings demonstrated that disruption of macrophage cell membrane integrity by C. albicans allows release of S. aureus from the macrophages; however, the process was contingent upon the ability of C. albicans to produce hyphae.
Conclusions: The combined findings from this study identify a novel cooperative immune evasion strategy between two important microbial pathogens. These findings are of clinical significance as this process may occur in a co-infected host. Therefore, understanding the dynamics of interactions between microbial pathogens and the host may lead to the development of novel therapeutic strategies to augment host immune defenses against invading microbial pathogens.