Bacterial carbohydrates trigger Candida albicans virulence

Grimes, Catherine LeimkuhlerThe human body is home to a diverse ecosystem containing trillions of microorganisms collectively referred to as the microbiome. Interactions between bacterial and fungal species have been correlated to the progression of cancer and Crohn’s disease. Despite the implications for human health, there is a lack of molecular understanding of how fungi recognize and respond to bacteria. It has been demonstrated that normally benign Candida albicans turns pathogenic when exposed to fragments of the bacterial cell wall. However, the molecular mechanism of this interaction is not well characterized. The work descried in this dissertation improves the molecular understanding of how Candida albicans is capable of recognizing molecules of bacterial origin and demonstrates for the first time that the Cyr1 can bind diverse bacterial carbohydrates to initiate hyphae growth. Importantly, the work described is the first to determine the strength of the interaction between Cyr1 and the peptidoglycan fragment, MTP, and the first report of Cyr1 binding the anthracycline, doxorubicin, and its carbohydrate moiety, daunosamine. ☐ In the larger biological landscape; this dissertation adds another level of molecular understanding used by the LRR domain. Purification of the LRR domain of Cyr1 allowed the successful development of a surface plasmon resonance assay to characterize the binding of bacterial derived carbohydrates. The mid-nanomolar binding affinities for MTP and daunosamine offer unique examples of strong protein-monosaccharide interactions. By comparing these molecular details, insight can be gained into how one domain can respond to a variety of ligands. Overall, this dissertation provides new tools to study the LRR domain and molecular level insight for carbohydrate – protein interactionsUniversity of Delaware, Department of Chemistry and BiochemistryPh.D