Helicobacter pylori is a highly successful pathogen uniquely adapted to colonize humans. Gastric infections with this bacterium can induce pathology ranging from chronic gastritis and peptic ulcers to gastric cancer. More virulent H. pylori isolates harbour numerous well-known adhesins (BabA/B, SabA, AlpA/B, OipA and HopZ) and the cag (cytotoxin-associated genes) pathogenicity island encoding a type IV secretion system (T4SS). The adhesins establish tight bacterial contact with host target cells and the T4SS represents a needle-like pilus device for the delivery of effector proteins into host target cells such as CagA. BabA and SabA bind to blood group antigen and sialylated proteins respectively, and a series of T4SS components including CagI, CagL, CagY and CagA have been shown to target the integrin β1 receptor followed by injection of CagA across the host cell membrane. The interaction of CagA with membrane-anchored phosphatidylserine may also play a role in the delivery process. While substantial progress has been made in our current understanding of many of the above factors, the host cell receptors for OipA, HopZ and AlpA/B during infection are still unknown. Here we review the recent progress in characterizing the interactions of the various adhesins and structural T4SS proteins with host cell factors. The contribution of these interactions to H. pylori colonization and pathogenesis is discussed.

Campylobacter jejuni is a common cause of serious diarrhoeal disease in humans, in contrast to the avian population, where exposure results in prolonged colonization at high density without disease. Colonized poultry present a significant source of infection to humans worldwide. The aim of this work was to compare the interaction of Campylobacter with primary intestinal cells from humans and poultry to identify factors that account for the divergent outcome following Campylobacter exposure. A primary intestinal cell model of Campylobacter infection was developed using cells grown from human and chicken intestinal biopsies. The cultured cells were infected with a number of strains of Campylobacter. Invasion by C. jejuni and the influence of intestinal mucus on Campylobacter internalization were studied by fluorescence microscopy and gentamicin protection assays. C. jejuni invaded primary human intestinal cells in a microtubule-, microfilament- and caveolin-dependent manner. Entry of C. jejuni into primary chicken intestinal cells also occurred. Chicken mucus, but not intestinal mucus of human origin, significantly reduced infection of primary human intestinal cells. Avian mucus appears to inhibit Campylobacter from interacting with epithelial cell surfaces.

Helicobacter pylori (H. pylori) colonizes the stomach of humans and causes chronic infection. The majority of bacteria live in the mucus layer overlying the gastric epithelial cells and only a small proportion of bacteria are found interacting with the epithelial cells. The bacteria living in the gastric mucus may act as a reservoir of infection for the underlying cells which is essential for the development of disease. Colonization of gastric mucus is likely to be key to the establishment of chronic infection. How H. pylori manages to colonise and survive in the hostile environment of the human stomach and avoid removal by mucus flow and killing by gastric acid is the subject of this review. We also discuss how bacterial and host factors may together go some way to explaining the susceptibility to colonization and the outcome of infection in different individuals. H. pylori infection of the gastric mucosa has become a paradigm for chronic infection. Understanding of why H. pylori is such a successful pathogen may help us understand how other bacterial species colonise mucosal surfaces and cause disease.

In this study, we tested the hypothesis that milk oligosaccharides may contribute not only to selective growth of bifidobacteria, but also to their specific adhesive ability. Human milk oligosaccharides (3′sialyllactose and 6′sialyllactose) and a commercial prebiotic (Beneo Orafti P95; oligofructose) were assayed for their ability to promote adhesion of Bifidobacterium longum subsp. infantis ATCC 15697 to HT-29 and Caco-2 human intestinal cells. Treatment with the commercial prebiotic or 3′sialyllactose did not enhance adhesion. However, treatment with 6′sialyllactose resulted in increased adhesion (4.7 fold), while treatment with a mixture of 3′- and 6′-sialyllactose substantially increased adhesion (9.8 fold) to HT-29 intestinal cells. Microarray analyses were subsequently employed to investigate the transcriptional response of B. longum subsp. infantis to the different oligosaccharide treatments. This data correlated strongly with the observed changes in adhesion to HT-29 cells. The combination of 3′- and 6′-sialyllactose resulted in the greatest response at the genetic level (both in diversity and magnitude) followed by 6′sialyllactose, and 3′sialyllactose alone. The microarray data was further validated by means of real-time PCR. The current findings suggest that the increased adherence phenotype of Bifidobacterium longum subsp. infantis resulting from exposure to milk oligosaccharides is multi-faceted, involving transcription factors, chaperone proteins, adhesion-related proteins, and a glycoside hydrolase. This study gives additional insight into the role of milk oligosaccharides within the human intestine and the molecular mechanisms underpinning host-microbe interactions.

The HT29MTXE12 (E12) cell line harbors an adherent mucus layer, providing a novel technique to model mucosal infection in vitro . In this study, we have characterized the interaction of Campylobacter jejuni with the E12 cell line and exploited its unique mucus layer to examine the potential efficacy of probiotic treatment to attenuate C. jejuni virulence properties. C. jejuni 81-176 colonized and reproduced in E12 mucus. Adhesion to and internalization of C. jejuni were enhanced in E12 cells harboring mucus compared to parental cells without mucus. Translocation of C. jejuni occurred at early time points following infection. C. jejuni aligned with tight junctions and colocalized with the tight junction protein occludin, suggesting a paracellular route of translocation. Probiotic strains Lactobacillus rhamnosus R0011, Lactobacillus helveticus R0052, Lactobacillus salivarius AH102, Bifidobacterium longum AH1205, a commercial combination of L. rhamnosus R0011 and L. helveticus R0052 (Lacidofil), and a cocktail consisting of L. rhamnosus , L. helveticus , and L. salivarius (RhHeSa) colonized E12 mucus and bound to underlying cells. Probiotics attenuated C. jejuni association with and internalization into E12 cells and translocation to the basolateral medium of transwells. Live bacteria and prolonged precolonization of E12 cells with probiotics were necessary for probiotic action. These results demonstrate the potential for E12 cells as a model of mucosal pathogenesis and provide a rationale for the further investigation of probiotics as prophylaxis against human campylobacteriosis.

Why Helicobacter pylori colonizes only gastric tissue is unknown. It is found on gastric mucus-secreting cells and in the overlying gastric mucus but not deep in gastric glands. This localization mirrors the expression of trefoil factor 1, TFF1. We hypothesized that H. pylori interacting with TFF1 could explain the tropism of this bacteria for gastric tissue. Recombinant human TFF1 expressed in Escherichia coli was purified by affinity chromatography, ion-exchange chromatography, and gel filtration. Binding of H. pylori was assessed by using flow cytometry and the BIAcore system, which allows real-time monitoring of molecular interactions. In flow cytometry, H. pylori bound to the TFF1 dimer, but Campylobacter jejuni strains and the laboratory strain of E. coli , HB101, did not bind. When the BIAcore system was used, H. pylori bound strongly to TFF1-coated dextran chips compared with uncoated chips. Binding was inhibited by a TFF1 monoclonal antibody and by soluble TFF1. H. pylori bound to porcine gastric mucin only if it was pretreated with TFF1. In conclusion, H. pylori interacts avidly with the dimeric form of TFF1, and this interaction enables binding to gastric mucin, suggesting that TFF1 may act as a receptor for the organism in vivo . This interaction may underline the previously unexplained tropism of this organism for gastric tissue and its colocalization with the gastric mucin MUC5AC.