Engineering Adhesion\nof the Probiotic Strain Escherichia coli Nissle to the Fungal Pathogen Candida albicans

Engineering live biotherapeutic products against fungal\npathogens\nsuch as Candida albicans has been suggested\nas a means to tackle the increasing threat of fungal infections and\nthe development of resistance to classical antifungal treatments.\nOne important challenge in the design of live therapeutics is to control\ntheir localization inside the human body. The specific binding capability\nto target organisms or tissues would greatly increase their effectiveness\nby increasing the local concentration of effector molecules at the\nsite of infection. In this study, we utilized surface display of carbohydrate\nbinding domains to enable the probiotic E. coli Nissle 1917 to adhere specifically to the pathogenic yeast Candida albicans. Binding was quantified using a\nnewly developed method based on the automated analysis of microscopic\nimages. In addition to a rationally selected chitin binding domain,\na synthetic peptide of identical length but distinct sequence also\nconferred binding. Efficient binding was specific to fungal hyphae,\nthe invasive form of C. albicans, while\nthe yeast form, as well as abiotic cellulose and PET particles, was\nonly weakly recognized.