Trends in Microbiology
ReviewMicrobial adhesins to gastrointestinal mucus
Section snippets
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.
References (82)
- et al.
The membrane-bound mucins: from cell signalling to transcriptional regulation and expression in epithelial cancers
Biochimie
(2010) Evidence of regio-specific glycosylation in human intestinal mucins: presence of an acidic gradient along the intestinal tract
J. Biol. Chem.
(2003)Crystal structure of a mucus-binding protein repeat reveals an unexpected functional immunoglobulin binding activity
J. Biol. Chem.
(2009)Internalins: a complex family of leucine-rich repeat-containing proteins in Listeria monocytogenes
Microbes Infect.
(2007)A collagen binding protein from Lactobacillus reuteri is part of an ABC transporter system?
FEMS Microbiol. Lett.
(1996)Characterization and purification of porcine small intestinal mucus receptor for Escherichia coli K88ac fimbrial adhesin
FEMS Immunol. Med. Microbiol.
(2000)Fimbriae extracts from enterotoxigenic Escherichia coli strains of bovine and porcine origin with K99 and/or F41 antigens
Vet. Microbiol.
(1996)Characterization of glycoprotein glycan receptors for Escherichia coli F17 fimbrial lectin
Microb. Pathog.
(1995)Structural basis for mechanical force regulation of the adhesin FimH via finger trap-like beta sheet twisting
Cell
(2010)Campylobacter flagella: not just for motility
Trends Microbiol.
(2007)