The effect of lung colonisation with Candida albicans on Staphylococcus aureus infection

Introduction: C. albicans is a commensal fungus found on mucosal surfaces, such as the gastrointestinal tract. The gram-positive bacterium S. aureus is also part of the human microbiome. In immunocompromised patients, both pathogens can cause severe systemic infections by disseminating via the gut or skin into the bloodstream. However, whereas S. aureus regularly causes pneumonia and disseminates from the lung into other parts of the body, C. albicans almost never causes invasive lung infections, despite massively colonising the lungs of mechanically ventilated patients.

Goals: We aim to determine the mechanism behind the different behaviour of C. albicans and S. aureus in the lung, and the effect of C. albicans on S. aureus infection.

Materials & Methods: We established a novel murine lung colonisation/infection model using 8-10-week-old Balb/c mice. Mice were administered 5x10⁶ colony forming units (CFUs) of C. albicans intranasally at day 0 and infected intranasally with 10⁸ CFUs S. aureus on day 1. At 24 and 48 hours post S. aureus infection, lung, liver and kidney bacterial/fungal burdens as well as lung and spleen immune responses were analysed.

Results: After intranasal administration, C. albicans numbers decreased while S. aureus numbers increased. S. aureus disseminated into the liver and kidney, whereas C. albicans did not. This mimics the clinical situation where C. albicans does not cause invasive infection via the lungs, but S. aureus does. S. aureus did not affect lung C. albicans loads, but C. albicans had a slight effect on S. aureus dissemination. Short-term C. albicans colonisation led to increased numbers of neutrophils, eosinophils and CD11b+ dendritic cells in the lung. Single cell RNA sequencing allowed us to analyse a wide range of lung myeloid cells including neutrophils, monocytes, inflammatory macrophages, natural killer cells, alveolar macrophages and dendritic cells.

Summary: We successfully established a mouse model of C. albicans and S. aureus colonisation/infection in the lungs. The effects of C. albicans on S. aureus infection will be further investigated, and mutant strains will be used to explore host-pathogen interactions.