Infection by <i>Helicobacter pylori</i> expressing the BabA adhesin is influenced by the secretor phenotype

Azevedo, Mafalda; Eriksson, Sara; Mendes, Nuno; Serpa, Jacinta; Figueiredo, Céu; Resende, LP; Ruvoën-Clouet, Nathalie; Haas, Rainer; Borén, Thomas; Pendu, Jacques Le; David, Leonor

doi:10.1002/path.2363

Cited by 71 publications

(21 citation statements)

References 39 publications

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“…Labeling with FITC and adhesion assays were performed as previously described [8,10,11]. Evaluation of bacterial binding was estimated by the number of adhered bacteria to superficial foveolar epithelium region under 200× magnification.…”

Section: Methodsmentioning

confidence: 99%

“…The blood group antigen binding adhesin (BabA) recognizes ABO(H)/Lewis b blood group antigens expressed in glycoproteins from the gastro-intestinal tract by secretor individuals [8–10], whereas the sialic acid binding adhesin (SabA) mediates bacterial attachment through binding to α2,3-sialylated structures, such as sialyl-Lewis a (sialyl-Le a ) and sialyl-Lewis x (sialyl-Le x ) carried by glycosphingolipids and glycoproteins [11]. The babA gene shares regions of high homology with the babB and babC genes.…”

Section: Introductionmentioning

confidence: 99%

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Helicobacter pylori chronic infection and mucosal inflammation switches the human gastric glycosylation pathways

Magalhães

Marcos-Pinto

Nairn

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Helicobacter pylori exploits host glycoconjugates to colonize the gastric niche. Infection can persist for decades promoting chronic inflammation, and in a subset of individuals lesions can silently progress to cancer. This study shows that H. pylori chronic infection and gastric tissue inflammation result in a remodeling of the gastric glycophenotype with increased expression of sialyl-Lewis a/x antigens due to transcriptional up-regulation of the B3GNT5, B3GALT5, and FUT3 genes. We observed that H. pylori infected individuals present a marked gastric local proinflammatory signature with significantly higher TNF-α levels and demonstrated that TNF-induced activation of the NF-kappaB pathway results in B3GNT5 transcriptional up-regulation. Furthermore, we show that this gastric glycosylation shift, characterized by increased sialylation patterns, favors SabA-mediated H. pylori attachment to human inflamed gastric mucosa. This study provides novel clinically relevant insights into the regulatory mechanisms underlying H. pylori modulation of host glycosylation machinery, and phenotypic alterations crucial for life-long infection. Moreover, the biosynthetic pathways here identified as responsible for gastric mucosa increased sialylation, in response to H. pylori infection, can be exploited as drug targets for hindering bacteria adhesion and counteract the infection chronicity.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Helicobacter pylori chronic infection and mucosal inflammation switches the human gastric glycosylation pathways

Magalhães

Marcos-Pinto

Nairn

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…H. pylori BabA binds with Leb and induces the double strand breaks in the host cells, which is thought to be independent of VacA, γ-glutamyl transpeptidase and the cag PAI[94]. However, it has been also confirmed that BabA-positive status of infecting strains is associated with CagA-positive, OipA-positive ( oipA “on”) and vacA s1 genotype for the development of intestinal metaplasia[95]. The infection with BabA-positive strains has been associated with the increased risk for development of peptic ulcer diseases in Western countries[41,96].…”

Section: Literature Searchmentioning

confidence: 99%

Helicobacter pyloriBabA in adaptation for gastric colonization

Ansari

Yamaoka

2017

WJG

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Helicobacter pylori (H. pylori) as a causative agent of gastric complications, is well adapted for the colonization of gastric mucosa. Although the infectious process depends on several factors, the adhesion to the gastric mucosa is the first and important step. Among several outer membrane proteins, BabA is one of the significant protein involving in many inflammatory processes in addition to its role in the attachment for the persistent colonization. We performed a PubMed search using the key words: “babA”, “pylori”, “gastric complications”, “homologous recombination”, “slipped strand mispairing”; a total of 249 articles were displayed. Of these we mainly focused on articles with the full text in English and published between 2005 and 2016. H. pylori BabA is involved in binding with receptors; however, its synthesis is regulated by phase variation. In this review we confirm that H. pylori babA can be modulated at the molecular and functional levels to adapt to the stress within the gastro-intestinal tract.

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“…BabA mediated attachment and development of disease are influenced by host expression of Lewis antigens, which is determined by a number of factors, including ABO blood type and secretor status30313233. The risk of ulcer is increased in individuals with blood group O, and in non-secretor individuals who do not express Le b and ABO antigens on gastric epithelial cells or on mucins3031323334.…”

mentioning

confidence: 99%

“…The risk of ulcer is increased in individuals with blood group O, and in non-secretor individuals who do not express Le b and ABO antigens on gastric epithelial cells or on mucins3031323334. Thus, disease outcome is related to both bacterial expression of the BabA adhesin and to ABO glycosylation on gastric epithelial cells and gastric mucins.…”

mentioning

confidence: 99%

Host Determinants of Expression of the Helicobacter pylori BabA Adhesin

Kable

Hansen

Styer

et al. 2017

Sci Rep

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Expression of the Helicobacter pylori blood group antigen binding adhesin A (BabA) is more common in strains isolated from patients with peptic ulcer disease or gastric cancer, rather than asymptomatic colonization. Here we used mouse models to examine host determinants that affect H. pylori BabA expression. BabA expression was lost by phase variation as frequently in WT mice as in RAG2−/− mice that do not have functional B or T cells, and in MyD88−/−, TLR2−/− and TLR4−/− mice that are defective in toll like receptor signaling. The presence of other bacteria had no effect on BabA expression as shown by infection of germ free mice. Moreover, loss of BabA expression was not dependent on Leb expression or the capacity of BabA to bind Leb. Surprisingly, gender was the host determinant most associated with loss of BabA expression, which was maintained to a greater extent in male mice and was associated with greater bacterial load. These results suggest the possibility that loss of BabA expression is not driven by adaptive immunity or toll-like receptor signaling, and that BabA may have other, unrecognized functions in addition to serving as an adhesin that binds Leb.

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Infection by Helicobacter pylori expressing the BabA adhesin is influenced by the secretor phenotype

Cited by 71 publications

References 39 publications

Helicobacter pylori chronic infection and mucosal inflammation switches the human gastric glycosylation pathways

Helicobacter pylori chronic infection and mucosal inflammation switches the human gastric glycosylation pathways

Helicobacter pyloriBabA in adaptation for gastric colonization

Host Determinants of Expression of the Helicobacter pylori BabA Adhesin

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