Helicobacter pylori Adapts to Chronic Infection and Gastric Disease via pH-Responsive BabA-Mediated Adherence

Jeanna A. Bugaytsova, Oscar Björnham, Yevgen A. Chernov, Pär Gideonsson, Sara Henriksson, Melissa Mendez, Rolf Sjöström, Jafar Mahdavi, Anna Shevtsova, Dag Ilver, Kristof Moonens, Macarena P. Quintana-Hayashi, Roman Moskalenko, Christopher Aisenbrey, Göran Bylund, Alexej Schmidt, Anna Åberg, Kristoffer Brännström, Verena Königer, Susanne VikströmLena Rakhimova, Anders Hofer, Johan Ögren, Hui Liu, Matthew D. Goldman, Jeannette M. Whitmire, Jörgen Ådén, Justine Younson, Charles G. Kelly, Robert H. Gilman, Abhijit Chowdhury, Asish K. Mukhopadhyay, G. Balakrish Nair, Konstantinos S. Papadakos, Beatriz Martinez-Gonzalez, Dionyssios N. Sgouras, Lars Engstrand, Magnus Unemo, Dan Danielsson, Sebastian Suerbaum, Stefan Oscarson, Ludmilla A. Morozova-Roche, Anders Olofsson, Gerhard Gröbner, Jan Holgersson, Anders Esberg, Nicklas Strömberg, Maréne Landström, Angela M. Eldridge, Brett A. Chromy, Lori M. Hansen, Jay V Solnick, Sara K. Lindén, Rainer Haas, Andre Dubois, D. Scott Merrell, Staffan Schedin, Han Remaut, Anna Arnqvist, Douglas E. Berg, Thomas Borén

Research output: Contribution to journalArticle

34 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)376-389
Number of pages14
JournalCell Host and Microbe
Volume21
Issue number3
DOIs
StatePublished - Mar 8 2017

Fingerprint

Stomach Diseases
Helicobacter pylori
Chronic Disease
Acids
Pylorus
Infection
Mucus
Blood Group Antigens
Gastric Mucosa
Genetic Recombination
Disease Progression
Stomach
Epithelial Cells
Mutation
Genes

Keywords

  • acid responsiveness
  • adaptation
  • blood group antigen-binding adhesion
  • diversity
  • gastric acidity
  • gastric cancer
  • Helicobacter pylori
  • multimerization
  • polymorphism
  • subpopulations

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology and Microbiology(all)
  • Cancer Research

Cite this

Bugaytsova, J. A., Björnham, O., Chernov, Y. A., Gideonsson, P., Henriksson, S., Mendez, M., ... Borén, 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. https://doi.org/10.1016/j.chom.2017.02.013

Helicobacter pylori Adapts to Chronic Infection and Gastric Disease via pH-Responsive BabA-Mediated Adherence. / Bugaytsova, Jeanna A.; Björnham, Oscar; Chernov, Yevgen A.; Gideonsson, Pär; Henriksson, Sara; Mendez, Melissa; Sjöström, Rolf; Mahdavi, Jafar; Shevtsova, Anna; Ilver, Dag; Moonens, Kristof; Quintana-Hayashi, Macarena P.; Moskalenko, Roman; Aisenbrey, Christopher; Bylund, Göran; Schmidt, Alexej; Åberg, Anna; Brännström, Kristoffer; Königer, Verena; Vikström, Susanne; Rakhimova, Lena; Hofer, Anders; Ögren, Johan; Liu, Hui; Goldman, Matthew D.; Whitmire, Jeannette M.; Ådén, Jörgen; Younson, Justine; Kelly, Charles G.; Gilman, Robert H.; Chowdhury, Abhijit; Mukhopadhyay, Asish K.; Nair, G. Balakrish; Papadakos, Konstantinos S.; Martinez-Gonzalez, Beatriz; Sgouras, Dionyssios N.; Engstrand, Lars; Unemo, Magnus; Danielsson, Dan; Suerbaum, Sebastian; Oscarson, Stefan; Morozova-Roche, Ludmilla A.; Olofsson, Anders; Gröbner, Gerhard; Holgersson, Jan; Esberg, Anders; Strömberg, Nicklas; Landström, Maréne; Eldridge, Angela M.; Chromy, Brett A.; Hansen, Lori M.; Solnick, Jay V; Lindén, Sara K.; Haas, Rainer; Dubois, Andre; Merrell, D. Scott; Schedin, Staffan; Remaut, Han; Arnqvist, Anna; Berg, Douglas E.; Borén, Thomas.

In: Cell Host and Microbe, Vol. 21, No. 3, 08.03.2017, p. 376-389.

Research output: Contribution to journalArticle

Bugaytsova, JA, Björnham, O, Chernov, YA, Gideonsson, P, Henriksson, S, Mendez, M, Sjöström, R, Mahdavi, J, Shevtsova, A, Ilver, D, Moonens, K, Quintana-Hayashi, MP, Moskalenko, R, Aisenbrey, C, Bylund, G, Schmidt, A, Åberg, A, Brännström, K, Königer, V, Vikström, S, Rakhimova, L, Hofer, A, Ögren, J, Liu, H, Goldman, MD, Whitmire, JM, Ådén, J, Younson, J, Kelly, CG, Gilman, RH, Chowdhury, A, Mukhopadhyay, AK, Nair, GB, Papadakos, KS, Martinez-Gonzalez, B, Sgouras, DN, Engstrand, L, Unemo, M, Danielsson, D, Suerbaum, S, Oscarson, S, Morozova-Roche, LA, Olofsson, A, Gröbner, G, Holgersson, J, Esberg, A, Strömberg, N, Landström, M, Eldridge, AM, Chromy, BA, Hansen, LM, Solnick, JV, Lindén, SK, Haas, R, Dubois, A, Merrell, DS, Schedin, S, Remaut, H, Arnqvist, A, Berg, DE & Borén, T 2017, 'Helicobacter pylori Adapts to Chronic Infection and Gastric Disease via pH-Responsive BabA-Mediated Adherence', Cell Host and Microbe, vol. 21, no. 3, pp. 376-389. https://doi.org/10.1016/j.chom.2017.02.013
Bugaytsova, Jeanna A. ; Björnham, Oscar ; Chernov, Yevgen A. ; Gideonsson, Pär ; Henriksson, Sara ; Mendez, Melissa ; Sjöström, Rolf ; Mahdavi, Jafar ; Shevtsova, Anna ; Ilver, Dag ; Moonens, Kristof ; Quintana-Hayashi, Macarena P. ; Moskalenko, Roman ; Aisenbrey, Christopher ; Bylund, Göran ; Schmidt, Alexej ; Åberg, Anna ; Brännström, Kristoffer ; Königer, Verena ; Vikström, Susanne ; Rakhimova, Lena ; Hofer, Anders ; Ögren, Johan ; Liu, Hui ; Goldman, Matthew D. ; Whitmire, Jeannette M. ; Ådén, Jörgen ; Younson, Justine ; Kelly, Charles G. ; Gilman, Robert H. ; Chowdhury, Abhijit ; Mukhopadhyay, Asish K. ; Nair, G. Balakrish ; Papadakos, Konstantinos S. ; Martinez-Gonzalez, Beatriz ; Sgouras, Dionyssios N. ; Engstrand, Lars ; Unemo, Magnus ; Danielsson, Dan ; Suerbaum, Sebastian ; Oscarson, Stefan ; Morozova-Roche, Ludmilla A. ; Olofsson, Anders ; Gröbner, Gerhard ; Holgersson, Jan ; Esberg, Anders ; Strömberg, Nicklas ; Landström, Maréne ; Eldridge, Angela M. ; Chromy, Brett A. ; Hansen, Lori M. ; Solnick, Jay V ; Lindén, Sara K. ; Haas, Rainer ; Dubois, Andre ; Merrell, D. Scott ; Schedin, Staffan ; Remaut, Han ; Arnqvist, Anna ; Berg, Douglas E. ; Borén, Thomas. / Helicobacter pylori Adapts to Chronic Infection and Gastric Disease via pH-Responsive BabA-Mediated Adherence. In: Cell Host and Microbe. 2017 ; Vol. 21, No. 3. pp. 376-389.
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AU - Bylund, Göran

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AU - Königer, Verena

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AU - Borén, Thomas

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