Interaction of microbes with mucus and mucins

Abstract

Due to the recent rapid expansion in our understanding of the composition of the gut microflora and the consequences of altering that composition the question of how bacteria colonise mucus layers and interact with components of mucus, such as mucin, is now receiving widespread attention. Using a combination of mucus secreting cells, and a novel mucin microarray platform containing purified native mucins from different sources we recently demonstrated that two gastrointestinal pathogens, Helicobacter pylori and Campylobacter jejuni, colonise mucus by different mechanisms. This result emphasizes the potential for even closely related bacteria to interact with mucus in divergent ways to establish successful infection. Expanding the use of the mucin arrays described in the study to other microorganisms, both pathogenic and commensal, should lead to the discovery of biologically important motifs in bacterial-host interactions and complement the use of novel in vitro cell models, such as mucus secreting cell lines. IntroductionMucosal surfaces serve as a portal of entry for the majority of infections that occur in humans and animals. All mucosal surfaces are covered in a layer of mucus. In the gastrointestinal tract this mucus is colonised by tens of trillions of commensal organisms, essential for the development and health of the host. Mucus in the murine colon and the stomach has been shown to consist of an inner closely adherent mucus layer and an outer less dense, loosely adherent layer. 1,2The small intestine has a single loosely adherent layer.2 In the colon the outer mucus layer is colonised by commensal bacteria while the inner mucus layer is devoid of microbiota.1 The protective function of the inner mucus layer can be disrupted in disease, allowing access of organisms to the underlying epithelium. For example, the mucus layer has been shown to be depleted in animal models of colitis, and also in humans with ulcerative colitis resulting in bacterial penetration of the inner layer. 3A complex, mutually dependent relationship is established between the gut microbiota and the human host from birth which persists throughout life. 4 Initial cross talk between the host and gut microbiota influences postnatal intestinal epithelial differentiation by altering gene expression and improves immune tolerance. 5-7The microbiota also provides other benefits to the host including priming of the immune system and protection of the mucosal surface by competing with invading pathogens for space, nutrients, and binding receptors. Recent advances in sequencing technology and metagenomics have revealed changes in the microbial population of the gut in both health and disease. Strikingly, these studies have shown that alterations in the composition of the gut microflora, sometimes referred to as dysbiosis, are associated with a number of chronic diseases including obesity, diabetes and inflammatory disease. 8-10 Interaction of microbes with mucus and mucins Recent developmentsJulie Naughton, 1,2 Gina Duggan, 1, 2 Billy Bourke, 1,...

The gut microbiome and the mechanism of surgical infection

“…Unfortunately, the H. pylori story was wholly dismissive of the potential role of the microbiome in the pathogenesis of ulcer disease that is now coming to light. The presence of an abundant and diverse microbiome within the stomach and duodenum may be an unrecognized defence factor in the pathogenesis of ulcer disease. This may even include the more common non‐steroidal anti‐inflammatory drug (NSAID)‐mediated ulcers that are rapidly becoming the most common cause of ulcer disease.…”

Use of Atomic Force Microscopy to Study the Multi-Modular Interaction of Bacterial Adhesins to Mucins

“…Methodologies to screen for bacterial adhesion to mucins have previously employed thin layer chromatography overlay [26], enzyme-linked immunosorbent assay [15], micro-titre plate assays [8,25,27], surface plasmon resonance [16,28,29,30,31], fluorescence spectroscopy [20], mucin microarrays [32], flow cytometry [33], and cell-based assays [26,34,35,36]. However, due to the complexity and diversity of mucin glycosylation, these methods typically provide qualitative binding data indicating only presence or absence of interaction.…”

Porcine Gastric Mucin Triggers Toxin Production of Enteropathogenic Bacillus cereus

“…strategies to antagonize the mucosal defenses. Helicobacter pylori, Campylobacter jejuni, Salmonella enterica serovar Typhimurium, Yersinia enterocolitica, enterohemorrhagic Escherichia coli (EHEC), enteropathogenic E. coli (EPEC), and others use the mucus glycoproteins for colonization by adhesion to the oligosaccharides (5,7,8). H. pylori, Salmonella, and C. jejuni are able to penetrate the mucus barrier (9,10).…”

“…H. pylori, Salmonella, and C. jejuni are able to penetrate the mucus barrier (9,10). Y. enterocolitica, Shigella, streptococci, and others produce glycosidases and proteases to degrade mucins (7,9). H. pylori can also induce downregulation of mucin gene expression or alteration of the glycosylation profile (7,11).…”

“…Y. enterocolitica, Shigella, streptococci, and others produce glycosidases and proteases to degrade mucins (7,9). H. pylori can also induce downregulation of mucin gene expression or alteration of the glycosylation profile (7,11). Another strategy is to avoid the mucin barrier by invading intestinal M cells or by disrupting the tight junctions between mucosal epithelial cells (5,9).…”