Trends in Microbiology
Volume 20, Issue 1, January 2012, Pages 30-39
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Review
Microbial adhesins to gastrointestinal mucus

https://doi.org/10.1016/j.tim.2011.10.001Get rights and content

The gastrointestinal tract (GIT) is lined by a layer of mucus formed by mucin glycoproteins. This layer constitutes a physical and chemical barrier between the intestinal contents and the underlying epithelia. In addition to this protective role, mucins harbor glycan-rich domains that provide preferential binding sites for pathogens and commensal bacteria. Although mucus–microbial interactions in the GIT play a crucial role in determining the outcome of relationships of both commensal and pathogens with the host, the adhesins and ligands involved in the interaction are poorly delineated. This review focuses on the current knowledge of microbial adhesins to gastrointestinal mucus and mucus components.

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Mucus and mucin glycans as receptors of gastrointestinal microbes

The mucus layer covering the gastrointestinal tract (GIT) is a biochemically complex medium, rich in glycoproteins, antimicrobial peptides, immunoglobulins and many other intestinal proteins, as well as lipids and electrolytes. The thickness of the mucus layer varies with the region of the GIT, but is thickest in the colon and rectum (Figure 1). The gastrointestinal mucus is divided into an outer loose layer which can be easily removed and an inner layer which is firmly attached to the

Mucus-binding proteins

Mucus-binding proteins (MUBs) have been revealed as one class of effector molecules involved in mechanisms of the adherence of lactobacilli, important commensal bacteria in the GIT, to the host [15]. MUBs are cell-surface proteins containing a typical signal peptide and a LPxTG anchoring motif in the C terminus for covalent attachment to the bacterial cell wall. MUBs are characterized by the presence of multiple Mub repeats, which share homology to the Pfam–MucBP (mucin-binding protein) domains

Multifunctional lactobacillus mucus adhesins

In addition to the structurally characterized MUB and MucBP proteins, multifunctional proteins have been involved in the adhesion of lactobacilli to gastrointestinal mucus [28], although biochemical characterization of the interaction to mucus and/or mucins is often preliminary. A collagen-binding protein (CnBP) of L. reuteri NCIB11951 [29], a mucus adhesion-promoting protein (MapA) of L. reuteri 104R [30] and mucus/mucin-binding protein (32-Mmubp) of Lactobacillus fermentum BCS87 [31] were all

Flagella, fimbriae and pili

Extracellular appendages such as flagella, pili and fimbriae (Box 3) play a major role in the attachment of bacteria to their host and have been implicated in mucus adhesion. Flagella are composed of several thousand copies of flagellin subunits and extensively studied in enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC), both of which cause diarrheal diseases and death worldwide. Recently, the EPEC E2348/69 (O127:H6) and EHEC EDL933 (O157:H7) flagella and their

Blood group antigen adhesins

Several human enteric pathogens bind to human histo-blood group antigens (HBGAs) expressed on the gut mucosa, including Campylobacter jejuni, Norwalk virus and Helicobacter pylori.

The best-characterized HBGA adhesin implicated in mucus binding is the blood group binding adhesin (BabA) from H. pylori. This bacterial pathogen lives in the mucus niche of the stomach and can cause gastric ulcers and cancer. The binding of H. pylori to gastric mucins through BabA and SabA (sialic acid-binding

Other examples of lectin-like mucus adhesins

Only limited information is available on microbial adhesins or lectins from gut microbes with demonstrated specificity towards mucin glycans. Entamoeba histolytica, a human intestinal protozoan parasite causing morbidity and mortality in developing countries, has a Gal/GalNAc cell-surface lectin that has been implicated in its binding to mucin oligosaccharides. This binding can be inhibited in vitro using purified rat colonic mucins [65]. The native protein is a 260-kDa heterodimer consisting

Concluding remarks and future directions

Microorganisms use adhesins to attach to their appropriate environmental niche. Our understanding of the interactions between commensals and pathogens to the mucus layer is increasing but remains incomplete. A widespread paradigm in the field of mucus and mucin biology is that microbes have evolved a multitude of lectins for recognition of the oligosaccharide structures present in mucins. However, little biochemically based evidence of binding to sugars supports this process. Most studies

Acknowledgments

This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC). Sabrina Etzold and Christine Fuell are acknowledged for their help with the preparation of some of the figures.

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