Analysis of a single Helicobacter pylori strain over a 10-year period in a primate model

Liu, Hui; Fero, Jutta; Mendez, Melissa; Carpenter, Beth M.; Servetas, Stephanie L.; Rahman, Arifur; Goldman, Matthew; Borén, Thomas; Salama, Nina R.; Merrell, D. Scott; Dubois, A.

doi:10.1016/j.ijmm.2015.03.002

Cited by 16 publications

(17 citation statements)

References 45 publications

(85 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar observations have been made by others3764. Clinical isolates of H. pylori also show remarkable diversity at the babA locus, which may encode a “specialist” adhesin that binds only blood group O/Le b , or a “generalist” that also binds blood group A/ALe b and B/BLe b 1920.…”

Section: Discussionsupporting

confidence: 80%

Host Determinants of Expression of the Helicobacter pylori BabA Adhesin

Kable

Hansen

Styer

et al. 2017

Sci Rep

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 80%

Host Determinants of Expression of the Helicobacter pylori BabA Adhesin

Kable

Hansen

Styer

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Yet this comes at the cost of an encounter with reactive oxygen species and other inflammatory mediators, as well as the risk of being shed into the lumen as the gastric epithelium is repopulated every few days. We and others have observed loss of BabA expression during experimental infections of mice, gerbils, and monkeys (23)(24)(25)37). While most strains recovered from humans express BabA, analysis of isolates recovered sequentially from the same individual over time demonstrates decreased Leb binding in nearly 25% of the strains (26).…”

Section: Discussionmentioning

confidence: 75%

Dynamic Expression of the BabA Adhesin and Its BabB Paralog during Helicobacter pylori Infection in Rhesus Macaques

et al. 2017

View full text Add to dashboard Cite

Most Helicobacter pylori strains express the BabA adhesin, which binds to ABO/Leb blood group antigens on gastric mucin and epithelial cells and is found more commonly in strains that cause peptic ulcers or gastric cancer, rather than asymptomatic infection. We and others have previously reported that in mice, gerbils, and rhesus macaques, expression of babA is lost, either by phase variation or by gene conversion, in which the babB paralog recombines into the babA locus. The functional significance of loss of babA expression is unknown. Here we report that in rhesus monkeys, there is independent selective pressure for loss of babA and for overexpression of BabB, which confers a fitness advantage. Surprisingly, loss of babA by phase variation or gene conversion is not dependent on the capacity of BabA protein to bind Leb, which suggests that it may have other, unrecognized functions. These findings have implications for the role of outer membrane protein diversity in persistent H. pylori infection.

show abstract

“…The presence of the H. pylori adhesins BabA and SabA hasbeen associated with a more severe disease outcome. However, in the H. pylori rhesus macaque infection model, BabA expression has been shown to decrease within weeks of infection due to selective pressure, although BabA was required for establishment of infection [20].…”

Section: Introductionmentioning

confidence: 99%

BabA-mediated adherence of pediatric ulcerogenic H. pylori strains to gastric mucins at neutral and acidic pH

et al. 2018

View full text Add to dashboard Cite

2018)BabA-mediated adherence of pediatric ulcerogenic H.pylori strains to gastric mucins at neutral and acidic pH, ABSTRACT Helicobacter pylori infection can result in non-ulcer dyspepsia (NUD), peptic ulcer disease (PUD), adenocarcinoma, and gastric lymphoma. H. pylori reside within the gastric mucus layer, mainly composed of mucins carrying an array of glycan structures that can serve as bacterial adhesion epitopes. The aim of the present study was to characterize the binding ability, adhesion modes, and growth of H. pylori strains from pediatric patients with NUD and PUD to gastric mucins. Our results showed an increased adhesion capacity of pediatric PUD H. pylori strains to human and rhesus monkey gastric mucins compared to the NUD strains both at neutral and acidic pH, regardless if the mucins were positive for Lewis b (Le b ), Sialyl-Lewis x (SLe x ) or LacdiNAc. In addition to babA positive strains being more common among PUD associated strains, H. pylori babA positive strains bound more avidly to gastric mucins than NUD babA positive strains at acidic pH. Binding to Le b was higher among babA positive PUD H. pylori strains compared to NUD strains at neutral, but not acidic, pH. PUD derived babA-knockout mutants had attenuated binding to mucins and Le b at acidic and neutral pH, and to SLe x and DNA at acidic pH. The results highlight the role of BabA-mediated adherence of pediatric ulcerogenic H. pylori strains, and points to a role for BabA in adhesion to charged structures at acidic pH, separate from its specific blood group binding activity. ARTICLE HISTORY

show abstract

Analysis of a single Helicobacter pylori strain over a 10-year period in a primate model

Cited by 16 publications

References 45 publications

Host Determinants of Expression of the Helicobacter pylori BabA Adhesin

Host Determinants of Expression of the Helicobacter pylori BabA Adhesin

Dynamic Expression of the BabA Adhesin and Its BabB Paralog during Helicobacter pylori Infection in Rhesus Macaques

BabA-mediated adherence of pediatric ulcerogenic H. pylori strains to gastric mucins at neutral and acidic pH

Contact Info

Product

Resources

About