To sugarcoat bacteria: Glycoengineering of lipooligosaccharides of bacteria with sialic acid derivatives

Abstract

This thesis focuses on two approaches from the interdisciplinary field of chemical biology. The first approach is related to glycobiology. Glycans are present on the surface of all cells, also on bacteria. Since these molecules are on the cell surface, they are often the first to interact with the environment and therefore also play an important role in many host-microbe interactions. An illustrative example of their importance is glycan mimicry of host glycans by bacteria, by which bacteria can interact with host receptors or avoid immune recognition by the host. An overview of bacteria that display glycan mimicry and chemical biology techniques to study this occurrence are presented in this thesis. In general, the study of glycans is ideally suited for chemical biology. The first chemical biology approach of this thesis describes two techniques to introduce N-acetylneuraminic acid on bacterial glycans: selective exoenzymatic labeling (SEEL) and native sialyltransferases. These new techniques could contribute to elucidating the interaction between sialylated bacterial pathogens and the immune system. It also highlights the promising future of glycoengineering for the study of bacterial glycobiology. The second chemical biology approach of this thesis focuses on a screen of small molecules that induce a biological process somatic embryogenesis in plants. In this process, a somatic cell is reprogrammed and can grow into a new embryo after the addition of a chemical inducer, compound 2,4-D. A structure-activity relationship of 2,4-D was established based on a screen of a library of 2,4-D analogues. This research contributed to understanding the role of 2,4-D and stress in the process of somatic embryogenesis in plants. Both approaches described in this thesis show that chemical biology is a powerful approach to study and influence biological processes on the molecular level.