Due to a limited set of antifungals available and problems in early diagnosis, invasive fungal infections caused by Candida species are among the most common hospital-acquired infections with staggering mortality rates. Here, we describe an engineered system able to sense and respond to the fungal pathogen Candida albicans, the most common cause of candidemia. In doing so, we identified hydroxyphenylacetic acid (HPA) as a novel molecule secreted by C. albicans. Furthermore, we engineered E. coli to be able to sense HPA produced by C. albicans. Finally, we constructed a sense-and-respond system by coupling the C. albicans sensor to the production of an inhibitor of hypha formation, thereby reducing filamentation, virulence factor expression, and fungal-induced epithelial damage. This system could be used as a basis for the development of novel prophylactic approaches to prevent fungal infections.
Keywords: Candida albicans; engineered probiotics; hypha inhibition; sense-and-respond.