Complex glycan catabolism by the human gut microbiota: the Bacteroidetes Sus-like paradigm

Abstract

Trillions of microbes inhabit the distal gut of adult humans. They have evolved to compete efficiently for nutrients, including a wide array of chemically diverse, complex glycans present in our diets, secreted by our intestinal mucosa, and displayed on the surfaces of other gut microbes. Here, we review how members of the Bacteroidetes, one of two dominant gut-associated bacterial phyla, process complex glycans using a series of similarly patterned, cell envelope-associated multiprotein systems. These systems provide insights into how gut, as well as terrestrial and aquatic, Bacteroidetes survive in highly competitive ecosystems.

FIGURE 1.

Functional model of glycan processing based on the eight-gene B. thetaiotaomicron starch utilization system (Sus). Individual starch processing steps are illustrated and numbered sequentially. Step 1, glycans transit through the surface capsular polysaccharide layer. The upper left inset shows a quick-freeze, deep-etch scanning electron micrograph of the capsule, highlighting its remarkably reticulated features (photograph courtesy of Robyn Roth and John Heuser). Step 2, glycans are bound by outer membrane-associated components such as SusD, which makes direct contacts with starch based on the three-dimensional structure of its helices. The upper right inset shows SusD binding to β-cyclodextrin (Protein Data Bank code 3CK8), a cyclic oligosaccharide that mimics the three-dimensional structure of starch. The arc of aromatic residues binding β-cyclodextrin is highlighted in yellow sticks, with the close-up view on the right displaying dashed lines for important hydrogen-bonding interactions. A single Ca²⁺ ion bound by SusD is shown as an orange sphere. Step 3, surface-bound glycans are degraded by outer membrane-associated glycoside hydrolases like SusG, generating smaller oligosaccharides that are transported across the outer membrane by SusC-like proteins. Step 4, oligosaccharides are degraded into their component mono- or disaccharides by periplasmic glycan-degrading enzymes such as SusA and SusB. Steps 5 and 6, liberated saccharides serve as signals for transcriptional regulators that activate PUL gene expression. Step 7, depolymerized sugars are imported across the cytoplasmic membrane.