Studying mixed-species biofilms of Candida albicans and Staphylococcus aureus using evolutionary game theory

Abstract

Mixed-species biofilms of Candida albicans and Staphylococcus aureus pose a significant clinical challenge due to their resistance to the human immune system and antimicrobial therapy. Using evolutionary game theory and nonlinear dynamics, we analyse the complex interactions between these organisms to understand their coexistence in the human host. We determine the Nash equilibria and evolutionary stable strategies of the game between C. albicans and S. aureus and point out different states of the mixed-species biofilm. Using replicator equations we study the fungal-bacterial interactions on a population level. Our focus is on the influence of available nutrients and the quorum sensing molecule farnesol, including the potential therapeutic use of artificially added farnesol. We also investigate the impact of the suggested scavenging of C. albicans hyphae by S. aureus. Contrary to common assumptions, we confirm the hypothesis that under certain conditions, mixed-species biofilms are not universally beneficial. Instead, different Nash equilibria occur depending on encountered conditions (i.e. varying farnesol levels, either produced by C. albicans or artificially added), including antagonism. We further show that the suggested scavenging of C. albicans’ hyphae by S. aureus does not influence the overall outcome of the game. Moreover, artificially added farnesol strongly affects the dynamics of the game, although its use as a medical adjuvant (add-on medication) may pose challenges.