Glycan Scavenging at the Cell Surface: The Bacteroidetes Sus-like paradigm

Microbiology;Gut Microbiome;Microbiology and Immunology;Health Sciences;Microbiology & Immunology

Foley, MattMartens, Eric Charles ;

University of Michigan

关键词: Microbiology;    Gut Microbiome;    Microbiology and Immunology;    Health Sciences;    Microbiology & Immunology;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/145817/mhfoley_1.pdf?sequence=2&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Resident bacteria in the densely populated human intestinal tract must efficiently compete for carbohydrate nutrition. The Bacteroidetes, a dominant bacterial phylum in the mammalian gut, encode a plethora of discrete polysaccharide utilization loci (PULs) that are selectively activated to facilitate glycan capture at the cell surface. The most well-studied PUL-encoded glycan uptake system is the starch utilization system (Sus) of Bacteroides thetaiotaomicron. The Sus includes the requisite proteins for binding and degrading starch at the surface of the cell preceding oligosaccharide transport across the outer membrane for further depolymerization to glucose in the periplasm. In the Sus of B. thetaiotaomicron, the well-characterized outer membrane proteins SusDEF and the α-amylase SusG each have unique structural features that allow them to interact with starch. The work presented here will address several important questions regarding how SusCDEFG and their homologs in other Sus-like systems work in relation to each other and with their cognate glycans to further develop what is known about the Sus-like paradigm of nutrient acquisition that is exclusive to the Gram-negative Bacteroidetes.Despite the apparent redundancy in starch-binding sites among these proteins, each has a distinct role during starch catabolism. In this thesis, new roles for the starch- binding protein SusE and SusF are described that further our understanding of maltooligosaccharide transport in the Sus. Sus outer membrane proteins dynamically interact and cooperate in the membrane. A new model is proposed for the formation of a Sus complex that assembles around the stationary starch-binding proteins SusE and SusF. Making comparisons across diverse PUL allow for the understanding of the conserved and divergent features of Sus-like systems. We demonstrate here that the Xyloglucan Utilization Locus of Bacteroides ovatus contains a hierarchy of xyloglucan- binding proteins that facilitate polysaccharide uptake and a cell surface GH9 plays a previously unappreciated role in xyloglucan capture. Lastly, the B. ovatus Mixed- Linkage Glucan Utilization Locus cell surface glycan-binding proteins are shown to display different contributions to mixed-linkage glucan capture and oligosaccharide uptake.These studies of polysaccharide-targeting systems provide mechanistic insights into the underpinnings of PUL-encoded glycan capture, and more broadly, how a fundamental phylum of the gut microbiome acquires carbohydrate nutrition.