Expression, purification and X-ray crystallographic analysis of the<i>Helicobacter pylori</i>blood group antigen-binding adhesin BabA

Subedi, Suresh; Moonens, Kristof; Romão, Ema; Lo, Alvin W.; Vandenbussche, Guy; Bugaytsova, Jeanna; Borén, Thomas; Remaut, Han

doi:10.1107/s2053230x14023188

Cited by 11 publications

(11 citation statements)

References 18 publications

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“…We previously found that residues 25–460 of the mature 721 residue BabA formed a stable, crystallizable fragment (hereafter dubbed BabAadhesin domain or BabA AD )(Subedi et al, 2014). Isothermal titration calorimetry (ITC) showed strain 17875 BabA AD bound Le b , with a monovalent binding interaction with a low micromolar dissociation constant (Kd) of 80.0 ± 7.1 μM (Figure 1B).…”

Section: Resultsmentioning

confidence: 99%

“…Crystal growth was facilitated with one of two nanobodies (Nb-ER14 or Nb-ER19) generated against native BabA purified from H. pylori found to stabilize the recombinant BabA AD fragment (Figure S1B) (Subedi et al, 2014). Both Nbs specifically bound to BabA-expressing H. pylori cells, demonstrating that the conformation of Nb-stabilized BabA AD is equivalent to that of native BabA in the bacterial outer membrane (Figure S1C).…”

Section: Resultsmentioning

confidence: 99%

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Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori

Moonens

Gideonsson

Subedi

et al. 2016

Cell Host & Microbe

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128

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Summary The Helicobacter pylori adhesin BabA binds mucosal ABO/Leb blood group (bg) carbohydrates. BabA facilitates bacterial attachment to gastric surfaces, increasing strain virulence and forming a recognized risk factor for peptic ulcers and gastric cancer. High sequence variation causes BabA functional diversity, but the underlying structural-molecular determinants are unknown. We generated X-ray structures of representative BabA isoforms that reveal a polymorphic, three-pronged Leb binding site. Two diversity loops, DL1 and DL2, provide adaptive control to binding affinity, notably ABO versus O bg preference. H. pylori strains can switch bg preference with single DL1 amino acid substitutions, and can coexpress functionally divergent BabA isoforms. The anchor point for receptor binding is the embrace of an ABO fucose residue by a disulfide-clasped loop, which is inactivated by reduction. Treatment with the redox-active pharmaceutic N-acetylcysteine lowers gastric mucosal neutrophil infiltration in H. pylori-infected Leb-expressing mice, providing perspectives on possible H. pylori eradication therapies.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori

Moonens

Gideonsson

Subedi

et al. 2016

Cell Host & Microbe

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128

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“…The crystal structures of BabA and of the homologous adhesin SabA was recently resolved [ 61 , 62 ] giving new insights into how H. pylori adhesion is mediated on sequence level. Comparing the BabA sequence to the SabA protein structure shows that there are several regions of high positive selection in the region where BabA and SabA do not share homology (Fig.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Latin American-specific BabA adhesin variant through whole genome sequencing of Helicobacter pylori patient isolates from Nicaragua

Thorell¹,

Hosseini²,

Gonzáles³

et al. 2016

BMC Evol Biol

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BackgroundHelicobacter pylori (H. pylori) is one of the most common bacterial infections in humans and this infection can lead to gastric ulcers and gastric cancer. H. pylori is one of the most genetically variable human pathogens and the ability of the bacterium to bind to the host epithelium as well as the presence of different virulence factors and genetic variants within these genes have been associated with disease severity. Nicaragua has particularly high gastric cancer incidence and we therefore studied Nicaraguan clinical H. pylori isolates for factors that could contribute to cancer risk.MethodsThe complete genomes of fifty-two Nicaraguan H. pylori isolates were sequenced and assembled de novo, and phylogenetic and virulence factor analyses were performed.ResultsThe Nicaraguan isolates showed phylogenetic relationship with West African isolates in whole-genome sequence comparisons and with Western and urban South- and Central American isolates using MLSA (Multi-locus sequence analysis). A majority, 77 % of the isolates carried the cancer-associated virulence gene cagA and also the s1/i1/m1 vacuolating cytotoxin, vacA allele combination, which is linked to increased severity of disease. Specifically, we also found that Nicaraguan isolates have a blood group-binding adhesin (BabA) variant highly similar to previously reported BabA sequences from Latin America, including from isolates belonging to other phylogenetic groups. These BabA sequences were found to be under positive selection at several amino acid positions that differed from the global collection of isolates.ConclusionThe discovery of a Latin American BabA variant, independent of overall phylogenetic background, suggests hitherto unknown host or environmental factors within the Latin American population giving H. pylori isolates carrying this adhesin variant a selective advantage, which could affect pathogenesis and risk for sequelae through specific adherence properties.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-016-0619-y) contains supplementary material, which is available to authorized users.

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“…Recently, additional evidence for this virulence role was provided by an epidemiological study that showed a significant association between the combination of OipA, BabA, and SabA and a diagnosis of H. pylori -associated gastric cancer (Su et al, 2016). However, recent investigations have reiterated that H. pylori BabA sequences, expression, and corresponding binding phenotypes are highly diverse and dynamic (Bugaytsova et al, 2017; Hansen et al, 2017; Kable et al, 2017; Moonens and Remaut, 2017; Subedi et al, 2014; Sweeney and Guillemin, 2016). Thus, caution is needed when suggesting an association between babA and clinical outcomes based on epidemiological studies.…”

Section: New Insights On H Pylori Virulence Factorsmentioning

confidence: 99%

Genetic populations and virulence factors of Helicobacter pylori

Kabamba

Tuan

Yamaoka

2018

Infection, Genetics and Evolution

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Helicobacter pylori is a bacterium that has infected more than half of the human population worldwide. This bacterium is closely associated with serious human diseases, such as gastric cancer, and identifying and understanding factors that predict bacterial virulence is a priority. In addition, this pathogen shows high genetic diversity and co-evolution with human hosts. H. pylori population genetics, therefore, has emerged as a tool to track human demographic history. As the number of genome sequences available is increasing, studies on the evolution and virulence of H. pylori are gaining momentum. This review article summarizes the most recent findings on H. pylori virulence factors and population genetics.

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Expression, purification and X-ray crystallographic analysis of theHelicobacter pyloriblood group antigen-binding adhesin BabA

Cited by 11 publications

References 18 publications

Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori

Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori

Identification of a Latin American-specific BabA adhesin variant through whole genome sequencing of Helicobacter pylori patient isolates from Nicaragua

Genetic populations and virulence factors of Helicobacter pylori

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