| 1. |
- Aspholm, Marina, et al.
(författare)
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SabA is the H. pylori hemagglutinin and is polymorphic in binding to sialylated glycans.
- 2006
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Ingår i: PLoS pathogens. - : Public Library of Science (PLoS). - 1553-7374 .- 1553-7366. ; 2:10
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Tidskriftsartikel (refereegranskat)abstract
- Adherence of Helicobacter pylori to inflamed gastric mucosa is dependent on the sialic acid-binding adhesin (SabA) and cognate sialylated/fucosylated glycans on the host cell surface. By in situ hybridization, H. pylori bacteria were observed in close association with erythrocytes in capillaries and post-capillary venules of the lamina propria of gastric mucosa in both infected humans and Rhesus monkeys. In vivo adherence of H. pylori to erythrocytes may require molecular mechanisms similar to the sialic acid-dependent in vitro agglutination of erythrocytes (i.e., sialic acid-dependent hemagglutination). In this context, the SabA adhesin was identified as the sialic acid-dependent hemagglutinin based on sialidase-sensitive hemagglutination, binding assays with sialylated glycoconjugates, and analysis of a series of isogenic sabA deletion mutants. The topographic presentation of binding sites for SabA on the erythrocyte membrane was mapped to gangliosides with extended core chains. However, receptor mapping revealed that the NeuAcalpha2-3Gal-disaccharide constitutes the minimal sialylated binding epitope required for SabA binding. Furthermore, clinical isolates demonstrated polymorphism in sialyl binding and complementation analysis of sabA mutants demonstrated that polymorphism in sialyl binding is an inherent property of the SabA protein itself. Gastric inflammation is associated with periodic changes in the composition of mucosal sialylation patterns. We suggest that dynamic adaptation in sialyl-binding properties during persistent infection specializes H. pylori both for individual variation in mucosal glycosylation and tropism for local areas of inflamed and/or dysplastic tissue.
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| 2. |
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| 3. |
- Bugaytsova, Jeanna, et al.
(författare)
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pH regulated H. pylori adherence : implications for persistent infection and disease
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Helicobacter pylori’s BabA adhesin binds strongly to gastric mucosal ABH/Leb glycans on the stomach epithelium and overlying mucus, materials continuously shed into the acidic gastric lumen. Here we report that this binding is acid labile, acid inactivation is fully reversible; and acid lability profiles vary with BabA sequence and correlate with disease patterns. Isogenic H. pylori strains from the gastric antrum and more acidic corpus were identified that differed in acid lability of receptor binding and in sequence near BabA’s carbohydrate binding domain. We propose that reversible acid inactivation of receptor binding helps H. pylori avoid clearance by mucosal shedding, and that strain differences in acid lability affect tissue tropism and the spectrum of associated gastric diseases.
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| 4. |
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| 5. |
- Garcia-Closas, Montserrat, et al.
(författare)
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Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics
- 2008
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 4:4, s. e1000054-
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Tidskriftsartikel (refereegranskat)abstract
- A three-stage genome-wide association study recently identified single nucleotide polymorphisms (SNPs) in five loci (fibroblast growth receptor 2 (FGFR2), trinucleotide repeat containing 9 (TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte-specific protein 1 (LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER-positive (per-allele OR (95%CI) = 1.31 (1.27-1.36)) than ER-negative (1.08 (1.03-1.14)) disease (P for heterogeneity = 10(-13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER-positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs (rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER-negative disease, the strongest association being for rs3803662 in TNRC9 (1.14 (1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis (per-allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER-positive and ER-negative disease are biologically distinct. Understanding the etiologic heterogeneity of breast cancer may ultimately result in improvements in prevention, early detection, and treatment.
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| 6. |
- Greiwe, Ansgar, et al.
(författare)
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Erfassung der Hauptreflektordeformation eines Radioteleskops durch UAV-gestützte Nahbereichsphotogrammetrie
- 2020
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Ingår i: Publikationen der Deutschen Gesellschaft für Photogrammetrie, Fernerkundung und Geoinformation e.V. ; :29, s. 346-357
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Konferensbidrag (refereegranskat)abstract
- Deformationen am Hauptreflektor eines Radioteleskops verursachen systematische Abweichungen in den Messungen und führen zu einer Verfälschung der abgeleiteten globalen Position und somit zu einem verzerrten Netzmaßstab im globalen geodätischen Bezugsrahmen. Um diese Systematiken zu minimieren, ist ein stabiler bzw. modellierbarer Strahlengang über den gesamten Arbeitsbereich des Teleskops notwendig. Zur messtechnischen Erfassung des Hauptreflektors konventioneller Radioteleskope werden gegenwärtig häufig Laserscanner verwendet, die eine Einzelpunktgenauigkeit von wenigen Millimetern erreichen. Für diesen Beitrag wurde erstmals das elevationsabhängige Verformungsverhalten eines modernen, kompakten VGOS-spezifizierten VLBI-Radioteleskops photogrammetrisch untersucht. Um den Hauptreflektor des Teleskops in mehreren Neigungen zu erfassen, erfolgte die photogrammetrische Datenerhebung durch ein Unmanned Aircraft Vehicle (UAV) als Sensorplattform für eine leichtgewichtige Kompaktkamera. Im Rahmen der Untersuchungen wurde eine Einzelpunktgenauigkeit von ca. 50 μm in 21 unterschiedlichen Bildverbänden erreicht.
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| 7. |
- Greiwe, Ansgar, et al.
(författare)
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Erfassung von Hauptreflektordeformationen an VGOS-Teleskopen mittels UAS
- 2020
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Ingår i: Photogrammetrie - Laserscanning - Optische 3D-Messtechnik: Beiträge der 19. Oldenburger 3D-Tage 2020. - 9783879076888
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Konferensbidrag (refereegranskat)abstract
- Das Verfahren zur Interferometrie auf langen Basislinien (VLBI) zählt zu den geodätischen Raumtechniken, die zur Realisierung eines erdfesten- als auch eines sternenfesten geodätischen Bezugssystems herangezogen werden. Messtechnische Untersuchungen von Hauptreflektoren konventioneller VLBI-Radioteleskope weisen ein elevationsabhängiges Eigenverformungsverhalten auf, die zu einer Variation der Brennweite von z.T. mehreren Zentimetern führt. Unkompensiert führen diese systematischen Verformungen zu einer Verzerrung der geschätzten Stationskoordinate, die u.U. den globalen Netzmaßstab verfälscht. Um das elevationsabhängige Verformungsverhalten eines kompakten 13 m VLBI-Radioteleskops zu untersuchen, werden für die Datenerhebung Messungen an diskreten Punkten auf dem Hauptreflektor in den unterschiedlichen Elevationsstellungen verwendet. Die geforderte Messgenauigkeit liegt hierbei unter 1 mm. Der naheliegende Einsatz der Nahbereichsphotogrammetrie per Kran wird hierbei durch die jeweilige Neigung des Hauptreflektors erschwert. Aus diesem Grunde wurde die Erfassung der Aufnahmen erstmals mit einem UAV und einer geeigneten Kamera durchgeführt. Im vorliegenden Beitrag werden das Messkonzept, die verwendete Kamera, erreichte Genauigkeiten und das Ergebnis der elevationsabhängigen Deformation vorgestellt.
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| 8. |
- Ishijima, Nozomi, et al.
(författare)
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BabA-mediated adherence is a potentiator of the Helicobacter pylori type IV secretion system activity
- 2011
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 286:28, s. 25256-25264
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Tidskriftsartikel (refereegranskat)abstract
- Chronic infection of Helicobacter pylori in the stomach mucosa with translocation of the bacterial cytotoxin-associated gene A (CagA) effector protein via the cag-Type IV secretion system (TFSS) into host epithelial cells are major risk factors for gastritis, gastric ulcers, and cancer. The blood group antigen-binding adhesin BabA mediates the adherence of H. pylori to ABO/Lewis b (Le(b)) blood group antigens in the gastric pit region of the human stomach mucosa. Here, we show both in vitro and in vivo that BabA-mediated binding of H. pylori to Le(b) on the epithelial surface augments TFSS-dependent H. pylori pathogenicity by triggering the production of proinflammatory cytokines and precancer-related factors. We successfully generated Le(b)-positive cell lineages by transfecting Le(b)-negative cells with several glycosyltransferase genes. Using these established cell lines, we found increased mRNA levels of proinflammatory cytokines (CCL5 and IL-8) as well as precancer-related factors (CDX2 and MUC2) after the infection of Le(b)-positive cells with WT H. pylori but not with babA or TFSS deletion mutants. This increased mRNA expression was abrogated when Le(b)-negative cells were infected with WT H. pylori. Thus, H. pylori can exploit BabA-Le(b) binding to trigger TFSS-dependent host cell signaling to induce the transcription of genes that enhance inflammation, development of intestinal metaplasia, and associated precancerous transformations.
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| 9. |
- Javaheri, Anahita, et al.
(författare)
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Helicobacter pylori adhesin HopQ engages in a virulence-enhancing interaction with human CEACAMs
- 2017
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Ingår i: Nature Microbiology. - : NATURE PUBLISHING GROUP. - 2058-5276. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori specifically colonizes the human gastric epithelium and is the major causative agent for ulcer disease and gastric cancer development. Here, we identify members of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family as receptors of H. pylori and show that HopQ is the surface-exposed adhesin that specifically binds human CEACAM1, CEACAM3, CEACAM5 and CEACAM6. HopQ-CEACAM binding is glycan-independent and targeted to the N-domain. H. pylori binding induces CEACAM1-mediated signalling, and the HopQ-CEACAM1 interaction enables translocation of the virulence factor CagA into host cells and enhances the release of pro-inflammatory mediators such as interleukin-8. Based on the crystal structure of HopQ, we found that a beta-hairpin insertion (HopQ-ID) in HopQ's extracellular 3+4 helix bundle domain is important for CEACAM binding. A peptide derived from this domain competitively inhibits HopQ-mediated activation of the Cag virulence pathway, as genetic or antibody-mediated abrogation of the HopQ function shows. Together, our data suggest the HopQ-CEACAM1 interaction to be a potentially promising novel therapeutic target to combat H. pylori-associated diseases.
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| 10. |
- Kickert, Conrad, et al.
(författare)
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Spatial dynamics of long-term urban retail decline in three transatlantic cities
- 2020
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Ingår i: Cities. - : Elsevier BV. - 0264-2751 .- 1873-6084. ; 107
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Tidskriftsartikel (refereegranskat)abstract
- This paper studies the effects of the centrality, connectivity and agglomeration of retail establishments on their long-term viability in three cities in the United States, United Kingdom and The Netherlands. As retail is declining in all three markets, there is a dearth of knowledge on the spatial patterns of this decline. This obstructs the substantiation of development decisions and public policy on urban retail retention and growth. Without knowing where stores are most at risk of closing, where can we decide to invest or divest? This paper uses a self-built dataset of store locations and store closures over the span of more than a century in the urban cores of Detroit, Michigan; Birmingham, England; and The Hague, The Netherlands. While taking different paths, all three cities have experienced significant retail decline over the past century. The probability of store closure over time is compared to the metric distance of stores to the retail center of gravity (centrality), store location along well-used streets as measured by their Choice value (connectivity), and the number of surrounding stores (agglomeration). These three comparisons are statistically analyzed using simple line regression, panel regression, and spatial autoregressive probit models. Across these models, store closure is most significantly affected by agglomeration, then by centrality, followed by connectivity. The significance of all three measures is strongest in The Hague, followed by Birmingham and Detroit – two cities that experienced large-scale urban renewal and socio-economic decline.
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| 11. |
- Magalhães, Ana, et al.
(författare)
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Fut2-null mice display an altered glycosylation profile and impaired BabA-mediated Helicobacter pylori adhesion to gastric mucosa
- 2009
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 0959-6658 .- 1460-2423. ; 19:12, s. 1525-1536
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Tidskriftsartikel (refereegranskat)abstract
- Glycoconjugates expressed on gastric mucosa play a crucial role in host-pathogen interactions. The FUT2 enzyme catalyzes the addition of terminal alpha(1,2)fucose residues, producing the H type 1 structure expressed on the surface of epithelial cells and in mucosal secretions of secretor individuals. Inactivating mutations in the human FUT2 gene are associated with reduced susceptibility to Helicobacter pylori infection. H. pylori infects over half the world's population and causes diverse gastric lesions, from gastritis to gastric cancer. H. pylori adhesion constitutes a crucial step in the establishment of a successful infection. The BabA adhesin binds the Le(b) and H type 1 structures expressed on gastric mucins, while SabA binds to sialylated carbohydrates mediating the adherence to inflamed gastric mucosa. In this study, we have used an animal model of nonsecretors, Fut2-null mice, to characterize the glycosylation profile and evaluate the effect of the observed glycan expression modifications in the process of H. pylori adhesion. We have demonstrated expression of terminal difucosylated glycan structures in C57Bl/6 mice gastric mucosa and that Fut2-null mice showed marked alteration in gastric mucosa glycosylation, characterized by diminished expression of alpha(1,2)fucosylated structures as indicated by lectin and antibody staining and further confirmed by mass spectrometry analysis. This altered glycosylation profile was further confirmed by the absence of Fucalpha(1,2)-dependent binding of calicivirus virus-like particles. Finally, using a panel of H. pylori strains, with different adhesin expression profiles, we have demonstated an impairment of BabA-dependent adhesion of H. pylori to Fut2-null mice gastric mucosa, whereas SabA-mediated binding was not affected.
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| 12. |
- Mahdavi, Jafar, et al.
(författare)
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The blood group antigen binding activity of the Helicobacter pylori baba adhesin is regulated by local ph and redox potential
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The blood group antigen hinding adhesin, BabA, which binds to fucosylated blood group antigens, such as the Lewis b (Leb) and H1 antigens constitutes one of the best recognized adhesin-receptor interactions that mediate adherence of Helicobacter pylori to the gastric epithelium. BabA belongs to a family of H. pylori outer membrane, proteins (HOPs), a group of some 30 proteins with most similar N- and C-terminal domains.We previously identified the babA1 and babA2 genes, where babA2 was found to encode the BabA adhesin in strain CCUG17875. Here, we confirmed the identity of the BabA protein by immunoblot-analysis, followed by MALDIT-OF MS analysis, which also provided molecular weight of the BabA polypeptide and the unique peptide sequences for BabA. Surprisingly, the BabA protein was found to be expressed 50-fold higher compared to the number of calculated bacterial Leb-binding sites.Furthermore, surface scan of the bacterial membrane by freeze fracture immuno-EM technique localized the BabA by immunogold labeling to the bacterial surface in numbers similar to the predicted binding sites. To help explain the binding results, crosslinker-analyses were performed which revealed that BabA form supra-molecular complexes on the bacterial surfaces. In addition, binding to the Lewis b antigen was shown to be pH dependent and took place over a broad pH range but binding activity was reversibly lost when approaching pH 3, i.e. conditions similar to the acidic gastric juice.The binding activity of the BabA adhesin was shown to be sensitive for reducing conditions, which suggests the presence of disulfide bond(s) close to the carbohydrate-binding domain. The dynamics of BabA in Leb-binding suggest that the bacterial adhesin is regulated by local variations in pH and redox potential, such as the pH gradient in the slimy mucus lining of the epithelium, and the reduced conditions of the inflamed gastric mucosa.
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| 13. |
- Majidi, Fatemeh, et al.
(författare)
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Clinical spectrum of primary adrenal lymphoma: results of a multicenter cohort study
- 2020
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Ingår i: European Journal of Endocrinology. - : BIOSCIENTIFICA LTD. - 0804-4643 .- 1479-683X. ; 183:4, s. 453-462
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: We sought to refine the clinical picture of primary adrenal lymphoma (PAL), a rare lymphoid malignancy with predominant adrenal manifestation and risk of adrenal insufficiency. Methods: Ninety-seven patients from 14 centers in Europe, Canada and the United States were included in this retrospective analysis between 1994 and 2017. Results: Of the 81 patients with imaging data, 19 (23%) had isolated adrenal involvement (iPAL), while 62 (77%) had additional extra-adrenal involvement (PAL+). Among patients who had both CT and PET scans, 18FDG-PET revealed extra-adrenal involvement not detected by CT scan in 9/18 cases (50%). The most common clinical manifestations were B symptoms (55%), fatigue (45%), and abdominal pain (35%). Endocrinological assessment was often inadequate. With a median follow-up of 41.6 months, 3-year progression-free (PFS) and overall (OS) survival rates in the entire cohort were 35.5% and 39.4%, respectively. The hazard ratios of iPAL for PFS and OS were 40.1 (95% CI: 2.63-613.7, P = 0.008) and 2.69 (95% CI: 0.61-11.89, P = 0.191), respectively. PFS was much shorter in iPAL vs PAL+ (median 4 months vs not reached, P = 0.006), and OS also appeared to be shorter (median 16 months vs not reached), but the difference did not reach statistical significance (P = 0.16). Isolated PAL was more frequent in females (OR = 3.81; P = 0.01) and less frequently associated with B symptoms (OR = 0.159; P = 0.004). Conclusion: We found unexpected heterogeneity in the clinical spectrum of PAL. Further studies are needed to clarify whether clinical distinction between iPAL and PAL+ is corroborated by differences in molecular biology.
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| 14. |
- Odenbreit, Stefan, et al.
(författare)
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Outer membrane protein expression profile in Helicobacter pylori clinical isolates
- 2009
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Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 77:9, s. 3782-3790
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Tidskriftsartikel (refereegranskat)abstract
- The gram-negative gastric pathogen Helicobacter pylori is equipped with an extraordinarily large set of outer membrane proteins (OMPs), whose role in the infection process is not well understood. The Hop (Helicobacter outer membrane porins) and Hor (Hop-related proteins) groups constitute a large paralogous family consisting of 33 members. The OMPs AlpA, AlpB, BabA, SabA, and HopZ have been identified as adhesins or adherence-associated proteins. To better understand the relevance of these and other OMPs during infection, we analyzed the expression of eight different omp genes (alpA, alpB, babA, babB, babC, sabA, hopM, and oipA) in a set of 200 patient isolates, mostly from symptomatic children or young adults. Virtually all clinical isolates produced the AlpA and AlpB proteins, supporting their essential function. All other OMPs were produced at extremely variable rates, ranging from 35% to 73%, indicating a function in close adaptation to the individual host or gastric niche. In 11% of the isolates, BabA was produced, and SabA was produced in 5% of the isolates, but the strains failed to bind their cognate substrates. Interleukin-8 (IL-8) expression in gastric cells was strictly dependent on the presence of the cag pathogenicity island, whereas the presence of OipA clearly enhanced IL-8 production. The presence of the translocated effector protein CagA correlated well with BabA and OipA production. In conclusion, we found unexpectedly diverse omp expression profiles in individual H. pylori strains and hypothesize that this reflects the selective pressure for adhesion, which may differ across different hosts as well as within an individual over time.
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| 15. |
- Olofsson, Annelie, et al.
(författare)
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Biochemical and functional characterization of Helicobacter pylori vesicles
- 2010
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Ingår i: Molecular Microbiology. - : Wiley. - 0950-382X .- 1365-2958. ; 77:6, s. 1539-1555
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori can cause peptic ulcer disease and/or gastric cancer. Adhesion of bacteria to the stomach mucosa is an important contributor to the vigor of infection and resulting virulence. H. pylori adheres primarily via binding of BabA adhesins to ABO/Lewis b (Leb) blood group antigens and the binding of SabA adhesins to sialyl-Lewis x/a (sLex/a) antigens. Similar to most Gram-negative bacteria, H. pylori continuously buds off vesicles and vesicles derived from pathogenic bacteria often include virulence-associated factors. Here we biochemically characterized highly purified H. pylori vesicles. Major protein and phospholipid components associated with the vesicles were identified with mass spectroscopy and NMR. A subset of virulence factors present was confirmed by immunoblots. Additional functional and biochemical analysis focused on the vesicle BabA and SabA adhesins and their respective interactions to human gastric epithelium. Vesicles exhibit heterogeneity in their protein composition, which were specifically studied in respect to the BabA adhesin. We also demonstrate that the oncoprotein, CagA, is associated with the surface of H. pylori vesicles. Thus, we have explored mechanisms for intimate H. pylori vesicle-host interactions and found that the vesicles carry effector-promoting properties that are important to disease development.
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| 16. |
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| 17. |
- Pivarcsi, Andor, et al.
(författare)
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Tumor immune escape by the loss of homeostatic chemokine expression.
- 2007
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 104:48, s. 19055-60
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Tidskriftsartikel (refereegranskat)abstract
- The novel keratinocyte-specific chemokine CCL27 plays a critical role in the organization of skin-associated immune responses by regulating T cell homing under homeostatic and inflammatory conditions. Here we demonstrate that human keratinocyte-derived skin tumors may evade T cell-mediated antitumor immune responses by down-regulating the expression of CCL27 through the activation of epidermal growth factor receptor (EGFR)-Ras-MAPK-signaling pathways. Compared with healthy skin, CCL27 mRNA and protein expression was progressively lost in transformed keratinocytes of actinic keratoses and basal and squamous cell carcinomas. In vivo, precancerous skin lesions as well as cutaneous carcinomas showed significantly elevated levels of phosphorylated ERK compared with normal skin, suggesting the activation of EGFR-Ras signaling pathways in keratinocyte-derived malignancies. In vitro, exogenous stimulation of the EGFR-Ras signaling pathway through EGF or transfection of the dominant-active form of the Ras oncogene (H-RasV12) suppressed whereas an EGFR tyrosine kinase inhibitor increased CCL27 mRNA and protein production in keratinocytes. In mice, neutralization of CCL27 led to decreased leukocyte recruitment to cutaneous tumor sites and significantly enhanced primary tumor growth. Collectively, our data identify a mechanism of skin tumors to evade host antitumor immune responses.
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| 18. |
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| 19. |
- Åberg, Anna, et al.
(författare)
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Helicobacter pylori adapts to chronic infection and gastric disease via ph-responsive baba-mediated adherence
- 2017
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Ingår i: Cell Host and Microbe. - : Elsevier BV. - 1931-3128 .- 1934-6069. ; 21:3, s. 376-389
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Tidskriftsartikel (refereegranskat)abstract
- The BabA adhesin mediates high-affinity binding of Helicobacter pylori to the ABO blood group antigen-glycosylated gastric mucosa. Here we show that BabA is acid responsive-binding is reduced at low pH and restored by acid neutralization. Acid responsiveness differs among strains; often correlates with different intragastric regions and evolves during chronic infection and disease progression; and depends on pH sensor sequences in BabA and on pH reversible formation of high-affinity binding BabA multimers. We propose that BabA's extraordinary reversible acid responsiveness enables tight mucosal bacterial adherence while also allowing an effective escape from epithelial cells and mucus that are shed into the acidic bactericidal lumen and that bio-selection and changes in BabA binding properties through mutation and recombination with babA-related genes are selected by differences among individuals and by changes in gastric acidity over time. These processes generate diverse H. pylori subpopulations, in which BabA's adaptive evolution contributes to H. pylori persistence and overt gastric disease.
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