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Mendez, Melissa
Alternative names
Publications (8 of 8) Show all publications
Bugaytsova, J. A., Björnham, O., Chernov, Y. A., Gideonsson, P., Henriksson, S., Mendez, M., . . . Boren, T. (2017). Helicobacter pylori Adapts to Chronic Infection and Gastric Disease via pH-Responsive BabA-Mediated Adherence. Cell Host and Microbe, 21(3), 376-389
Open this publication in new window or tab >>Helicobacter pylori Adapts to Chronic Infection and Gastric Disease via pH-Responsive BabA-Mediated Adherence
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2017 (English)In: Cell Host and Microbe, ISSN 1931-3128, E-ISSN 1934-6069, Vol. 21, no 3, p. 376-389Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
CELL PRESS, 2017
National Category
Microbiology in the medical area Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-132788 (URN)10.1016/j.chom.2017.02.013 (DOI)000396375600023 ()28279347 (PubMedID)
Available from: 2017-05-11 Created: 2017-05-11 Last updated: 2019-05-24Bibliographically approved
Moonens, K., Gideonsson, P., Subedi, S., Bugaytsova, J., Romao, E., Mendez, M., . . . Remaut, H. (2016). Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori. Cell Host and Microbe, 19(1), 55-66
Open this publication in new window or tab >>Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori
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2016 (English)In: Cell Host and Microbe, ISSN 1931-3128, E-ISSN 1934-6069, Vol. 19, no 1, p. 55-66Article in journal (Refereed) Published
Abstract [en]

The Helicobacter pylori adhesin BabA binds mucosal ABO/Le b 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 Le(b) 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 Le(b)-expressing mice, providing perspectives on possible H. pylori eradication therapies.

National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-117839 (URN)10.1016/j.chom.2015.12.004 (DOI)000369839900010 ()26764597 (PubMedID)
Available from: 2016-04-04 Created: 2016-03-04 Last updated: 2018-06-07Bibliographically approved
Liu, H., Fero, J. B., Mendez, M., Carpenter, B. M., Servetas, S. L., Rahman, A., . . . Dubois, A. (2015). Analysis of a single Helicobacter pylori strain over a 10-year period in a primate model. International Journal of Medical Microbiology, 305(3), 392-403
Open this publication in new window or tab >>Analysis of a single Helicobacter pylori strain over a 10-year period in a primate model
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2015 (English)In: International Journal of Medical Microbiology, ISSN 1438-4221, E-ISSN 1618-0607, Vol. 305, no 3, p. 392-403Article in journal (Refereed) Published
Abstract [en]

Helicobacter pylori from different individuals exhibits substantial genetic diversity. However, the kinetics of bacterial diversification after infection with a single strain is poorly understood. We investigated evolution of H. pylori following long-term infection in the primate stomach; Rhesus macaques were infected with H. pylori strain USU101 and then followed for 10 years. H. pylori was regularly cultured from biopsies, and single colony isolates were analyzed. At 1-year, DNA fingerprinting showed that all output isolates were identical to the input strain; however, at 5-years, different H. pylori fingerprints were observed. Microarray-based comparative genomic hybridization revealed that long term persistence of USU101 in the macaque stomach was associated with specific whole gene changes. Further detailed investigation showed that levels of the BabA protein were dramatically reduced within weeks of infection. The molecular mechanisms behind this reduction were shown to include phase variation and gene loss via intragenomic rearrangement, suggesting strong selective pressure against BabA expression in the macaque model. Notably, although there is apparently strong selective pressure against babA, babA is required for establishment of infection in this model as a strain in which babA was deleted was unable to colonize experimentally infected macaques.

Keywords
Evolution, babA, Helicobacter pylori, Colonization, Outer membrane protein
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-106142 (URN)10.1016/j.ijmm.2015.03.002 (DOI)000354583900014 ()25804332 (PubMedID)
Available from: 2015-07-13 Created: 2015-07-09 Last updated: 2018-06-07Bibliographically approved
Méndez, M. (2014). Diversity and adaptation in the adherence properties of Helicobacter pylori. (Doctoral dissertation). Umeå: Umeå universitet
Open this publication in new window or tab >>Diversity and adaptation in the adherence properties of Helicobacter pylori
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2014. p. 39
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1602
Keywords
Helicobacter pylori, transmission, phylogeny, native populations, bacterial adherence, BabA adhesin, receptor specificity, functional polymorphism, genetic diversity, adaptation
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-84597 (URN)978-91-7459-734-9 (ISBN)
Public defence
2014-01-24, Naturvetarhuset, N300, Umeå universitet, Umeå, 10:00 (English)
Opponent
Supervisors
Available from: 2014-01-10 Created: 2014-01-10 Last updated: 2018-06-08Bibliographically approved
Kersulyte, D., Kalia, A., Gilman, R. H., Mendez, M., Herrera, P., Cabrera, L., . . . Berg, D. E. (2010). Helicobacter pylori from Peruvian amerindians: traces of human migrations in strains from remote Amazon, and genome sequence of an Amerind strain. PLoS ONE, 5(11), e15076
Open this publication in new window or tab >>Helicobacter pylori from Peruvian amerindians: traces of human migrations in strains from remote Amazon, and genome sequence of an Amerind strain
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2010 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 5, no 11, p. e15076-Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The gastric pathogen Helicobacter pylori is extraordinary in its genetic diversity, the differences between strains from well-separated human populations, and the range of diseases that infection promotes.

PRINCIPAL FINDINGS: Housekeeping gene sequences from H. pylori from residents of an Amerindian village in the Peruvian Amazon, Shimaa, were related to, but not intermingled with, those from Asia. This suggests descent of Shimaa strains from H. pylori that had infected the people who migrated from Asia into The Americas some 15,000+ years ago. In contrast, European type sequences predominated in strains from Amerindian Lima shantytown residents, but with some 12% Amerindian or East Asian-like admixture, which indicates displacement of ancestral purely Amerindian strains by those of hybrid or European ancestry. The genome of one Shimaa village strain, Shi470, was sequenced completely. Its SNP pattern was more Asian- than European-like genome-wide, indicating a purely Amerind ancestry. Among its unusual features were two cagA virulence genes, each distinct from those known from elsewhere; and a novel allele of gene hp0519, whose encoded protein is postulated to interact with host tissue. More generally, however, the Shi470 genome is similar in gene content and organization to those of strains from industrialized countries.

CONCLUSIONS: Our data indicate that Shimaa village H. pylori descend from Asian strains brought to The Americas many millennia ago; and that Amerind strains are less fit than, and were substantially displaced by, hybrid or European strains in less isolated communities. Genome comparisons of H. pylori from Amerindian and other communities should help elucidate evolutionary forces that have shaped pathogen populations in The Americas and worldwide.

National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-83678 (URN)10.1371/journal.pone.0015076 (DOI)21124785 (PubMedID)
Available from: 2014-01-09 Created: 2013-12-03 Last updated: 2018-06-08Bibliographically approved
Herrera, P. M., Mendez, M., Velapatiño, B., Santivañez, L., Balqui, J., Finger, S. A., . . . Berg, D. E. (2008). DNA-level diversity and relatedness of Helicobacter pylori strains in shantytown families in Peru and transmission in a developing-country setting.. Journal of Clinical Microbiology, 46(12), 3912-3918
Open this publication in new window or tab >>DNA-level diversity and relatedness of Helicobacter pylori strains in shantytown families in Peru and transmission in a developing-country setting.
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2008 (English)In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 46, no 12, p. 3912-3918Article in journal (Refereed) Published
Abstract [en]

The efficiency of transmission of a pathogen within families compared with that between unrelated persons can affect both the strategies needed to control or eradicate infection and how the pathogen evolves. In industrialized countries, most cases of transmission of the gastric pathogen Helicobacter pylori seems to be from mother to child. An alternative model, potentially applicable among the very poor in developing countries, where infection is more common and the sanitary infrastructure is often deficient, invokes frequent transmission among unrelated persons, often via environmental sources. In the present study, we compared the genotypes of H. pylori from members of shantytown households in Peru to better understand the transmission of H. pylori in developing-country settings. H. pylori cultures and/or DNAs were obtained with informed consent by the string test (a minimally invasive alternative to endoscopy) from at least one child and one parent from each of 62 families. The random amplified polymorphic DNA fingerprints of 57 of 81 (70%) child-mother strain pairs did not match, nor did the diagnostic gene sequences (>1% DNA sequence difference), independent of the child's age (range, 1 to 39 years). Most strains from siblings or other paired family members were also unrelated. These results suggest that H. pylori infections are often community acquired in the society studied. Transmission between unrelated persons should facilitate the formation of novel recombinant genotypes by interstrain DNA transfer and selection for genotypes that are well suited for individual hosts. It also implies that the effective prevention of H. pylori infection and associated gastroduodenal disease will require anti-H. pylori measures to be applied communitywide.

National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-84596 (URN)10.1128/JCM.01453-08 (DOI)18842944 (PubMedID)
Available from: 2014-01-09 Created: 2014-01-09 Last updated: 2018-06-08Bibliographically approved
Méndez, M., Kersulyte, D., Sjöström, R., Balqui, J., Velapatiño, B., Cabrera, L., . . . Borén, T.Functional polymorphism and blood group tropism in Helicobacter pylori BabA from remote Amazon diasporas.
Open this publication in new window or tab >>Functional polymorphism and blood group tropism in Helicobacter pylori BabA from remote Amazon diasporas
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(English)Manuscript (preprint) (Other academic)
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-84593 (URN)
Available from: 2014-01-09 Created: 2014-01-09 Last updated: 2018-06-08Bibliographically approved
Bugaytsova, J., Björnhamn, O., Henriksson, S., Johansson, P., Mendez, M., Sjöström, R., . . . Borén, T. pH regulated H. pylori adherence: implications for persistent infection and disease.
Open this publication in new window or tab >>pH regulated H. pylori adherence: implications for persistent infection and disease
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

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.

National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-21487 (URN)
Available from: 2009-04-14 Created: 2009-04-14 Last updated: 2018-06-09Bibliographically approved
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