Elucidating novel immune evasion strategies of Candida albicans

Innate immunity is key for protection against fungal pathogens, providing selective pressure on fungi to evolve immune evasion strategies. Candida albicans is a commensal and opportunistic fungal pathogen, that can evade the immune system by remodelling its cell wall to prevent recognition of glucan, or through Factor H dependent inactivation of the alternative complement system. We have identified that other environmental conditions encountered in the host promote immune evasion of C. albicans independently of glucan remodelling and Factor H binding, suggesting that C. albicans has evolved other immune evasion strategies to aid its survival in the host. Using in vitro screens and fungal molecular biology, in combination with unbiased in vivo approaches, we will determine which host niches promote immune evasion and underpin their molecular mechanisms. Once mapped, we will manipulate fungal immune evasion using mutants with reduced or enhanced evasion capacity to understand their impact on the composition of the microbiome, and the role of these strategies in clinically relevant scenarios. This all-encompassing project will provide a step-change in our understanding of fungal pathogenicity and will lead to the identification of new therapeutic targets which can be exploited to restore immune recognition and prevent infection.