Lactobacillus adhesion to mucus

Abstract

Mucus provides protective functions in the gastrointestinal tract and plays an important role in the adhesion of microorganisms to host surfaces. Mucin glycoproteins polymerize, forming a framework to which certain microbial populations can adhere, including probiotic Lactobacillus species. Numerous mechanisms for adhesion to mucus have been discovered in lactobacilli, including partially characterized mucus binding proteins. These mechanisms vary in importance with the in vitro models studied, which could significantly affect the perceived probiotic potential of the organisms. Understanding the nature of mucus-microbe interactions could be the key to elucidating the mechanisms of probiotic adhesion within the host.

Keywords: adhesion; MUC2; MucBP; binding; lactobacillus; mucin; mucus; probiotics.

Figure 1

Diagram of the MUC2 protein core. The protein termini contain cysteine-rich regions homologous to von Willebrand Factor (vWF) domains (a); The N-terminal regions of MUC2 proteins contain vWF domain homologs D1, D2, D′, and D3 and the C-terminal regions contain vWF domain homologs D4, B, C, and CK. These terminal domains are responsible for the extensive polymerization between mucin monomers, along with the cysteine rich interruptions between glycosylated tandem repeats (b); The first of two repetitive domains (c) contains 21 repeats of an irregular motif, whereas the second domain (d) is formed of 50-115 tandem 23aa motifs (PTTTPITTTTTVTPTPTPTGTQT). Threonines in the repeats are O-glycosylated, forming a densely packed envelope of short, branched carbohydrate chains surrounding these regions.

Figure 2

Simplified histological cross-section of microbial adhesion to the colonic mucosal surface at various magnifications. (a) The layer of mucus atop colonic epithelial villi. Goblet cells can be seen interspersed throughout the columnar enterocytes, producing secretory mucin that makes up the gel matrix. The microbial communities residing in and on top of the mucus layer can only be found at substantial concentrations in the outermost regions of the mucus; (b) The mucus-bacteria interface. The mucin molecules polymerize to form the mucus layer matrix to which cells adhere. Extensive disulfide bonding between cysteine-rich regions of the mucin protein cores creates the characteristic viscoelastic properties of mucus. Oligosaccharide modifications of mucin protein cores form “bottle-brush” regions providing substrate for adhesion to binding proteins on bacterial cell surfaces; (c) A proposed molecular mechanism of adhesion. Evidence suggests that putative mucin-binding proteins anchored to the bacterial cell wall may interact with the glycosyl modifications of the mucin proteins to promote adhesion of the cell to the mucus layer. Mucin oligosaccharide structures vary due to tissue and cell-specific glycosyltransferase expression levels, so the specificity of particular oligosaccharide moieties may lead to preferential binding of particular bacteria to different host niches.