Mucins and the Microbiome

Abstract

Generating the barriers that protect our inner surfaces from bacteria and other challenges requires large glycoproteins called mucins. These come in two types, gel-forming and transmembrane, all characterized by large, highly O-glycosylated mucin domains that are diversely decorated by Golgi glycosyltransferases to become extended rodlike structures. The general functions of mucins on internal epithelial surfaces are to wash away microorganisms and, even more importantly, to build protective barriers. The latter function is most evident in the large intestine, where the inner mucus layer separates the numerous commensal bacteria from the epithelial cells. The host's conversion of MUC2 to the outer mucus layer allows bacteria to degrade the mucin glycans and recover the energy content that is then shared with the host. The molecular nature of the mucins is complex, and how they construct the extracellular complex glycocalyx and mucus is poorly understood and a future biochemical challenge.

Keywords: bacteria; carbohydrate; glycan; intestine; mucus; saccharide.

Figure 1

Gel-forming and transmembrane mucins have mucin domains encoded by PTS sequences.

Figure 2

Mucin O-glycosylation. a) Major O-glycan core structures. b) Chromatograms and major structure of major O-glycans of mouse and human MUC2 mucin.

Figure 3

Domains of the four human gel-forming mucins.

Figure 4

Evolution of mucins and their major domains

Figure 5

The mucus system of the normal and diseased respiratory tract. a) The submucosal gland is a molecular machine for the generation of mucin MUC5B based bundles. b) The bundles are transported on the tracheobronchial surface by the beating cilia and moving ASL cephalically. Bacteria are collected by the bundles sweeping over the surface. c) An attached mucus layer is formed by the MUC5AC and MUC5B mucins in diseased lungs and by this help to protect the epithelial cells from bacteria.

Figure 6

The mucus system and bacteria of the normal colon. a) Goblet cells are assembling MUC2 into large polymers that upon secretion generate large net-like structures that are staggerd on below each other to form the attached inner mucus layer. The pore sizes of this inner layer is small and consequently keep bacteria away from the epithelial cells. At the interphase to the outer mucus layer, the pore sizes are increased allowing bacteria to enter and degrade the mucin glycan to generate short fatty acids (SCFA) feeding the epithelial cells. b) Ulcerative colitis is initiated when the inner mucus layer (first defense line, 1), the sentinel Goblet Cell (second defense line, 2), and a potential third defense line (3) is failing and bacteria reach the subepithelial immune system.