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 Vikström; Lena 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

doi:10.1016/j.chom.2017.02.013

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

Bloomberg School of Public Health

Research output: Contribution to journal › Article › peer-review

56 Scopus citations

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 language	English (US)
Pages (from-to)	376-389
Number of pages	14
Journal	Cell Host and Microbe
Volume	21
Issue number	3
DOIs	https://doi.org/10.1016/j.chom.2017.02.013
State	Published - Mar 8 2017

Keywords

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

ASJC Scopus subject areas

Parasitology
Microbiology
Virology

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10.1016/j.chom.2017.02.013

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Bugaytsova, J. A., Björnham, O., Chernov, Y. A., Gideonsson, P., Henriksson, S., Mendez, M., Sjöström, R., Mahdavi, J., Shevtsova, A., Ilver, D., Moonens, K., Quintana-Hayashi, M. P., Moskalenko, R., Aisenbrey, C., Bylund, G., Schmidt, A., Åberg, A., Brännström, K., Königer, V., ... 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

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

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

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.",

keywords = "Helicobacter pylori, acid responsiveness, adaptation, blood group antigen-binding adhesion, diversity, gastric acidity, gastric cancer, multimerization, polymorphism, subpopulations",

author = "Bugaytsova, {Jeanna A.} and Oscar Bj{\"o}rnham and Chernov, {Yevgen A.} and P{\"a}r Gideonsson and Sara Henriksson and Melissa Mendez and Rolf Sj{\"o}str{\"o}m and Jafar Mahdavi and Anna Shevtsova and Dag Ilver and Kristof Moonens and Quintana-Hayashi, {Macarena P.} and Roman Moskalenko and Christopher Aisenbrey and G{\"o}ran Bylund and Alexej Schmidt and Anna {\AA}berg and Kristoffer Br{\"a}nnstr{\"o}m and Verena K{\"o}niger and Susanne Vikstr{\"o}m and Lena Rakhimova and Anders Hofer and Johan {\"O}gren and Hui Liu and Goldman, {Matthew D.} and Whitmire, {Jeannette M.} and J{\"o}rgen {\AA}d{\'e}n and Justine Younson and Kelly, {Charles G.} and Gilman, {Robert H.} and Abhijit Chowdhury and Mukhopadhyay, {Asish K.} and Nair, {G. Balakrish} and Papadakos, {Konstantinos S.} and Beatriz Martinez-Gonzalez and Sgouras, {Dionyssios N.} and Lars Engstrand and Magnus Unemo and Dan Danielsson and Sebastian Suerbaum and Stefan Oscarson and Morozova-Roche, {Ludmilla A.} and Anders Olofsson and Gerhard Gr{\"o}bner and Jan Holgersson and Anders Esberg and Nicklas Str{\"o}mberg and Mar{\'e}ne Landstr{\"o}m and Eldridge, {Angela M.} and Chromy, {Brett A.} and Hansen, {Lori M.} and Solnick, {Jay V.} and Lind{\'e}n, {Sara K.} and Rainer Haas and Andre Dubois and Merrell, {D. Scott} and Staffan Schedin and Han Remaut and Anna Arnqvist and Berg, {Douglas E.} and Thomas Bor{\'e}n",

note = "Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",

year = "2017",

month = mar,

day = "8",

doi = "10.1016/j.chom.2017.02.013",

language = "English (US)",

volume = "21",

pages = "376--389",

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T1 - Helicobacter pylori Adapts to Chronic Infection and Gastric Disease via pH-Responsive BabA-Mediated Adherence

AU - Bugaytsova, Jeanna A.

AU - Björnham, Oscar

AU - Chernov, Yevgen A.

AU - Gideonsson, Pär

AU - Henriksson, Sara

AU - Mendez, Melissa

AU - Sjöström, Rolf

AU - Mahdavi, Jafar

AU - Shevtsova, Anna

AU - Ilver, Dag

AU - Moonens, Kristof

AU - Quintana-Hayashi, Macarena P.

AU - Moskalenko, Roman

AU - Aisenbrey, Christopher

AU - Bylund, Göran

AU - Schmidt, Alexej

AU - Åberg, Anna

AU - Brännström, Kristoffer

AU - Königer, Verena

AU - Vikström, Susanne

AU - Rakhimova, Lena

AU - Hofer, Anders

AU - Ögren, Johan

AU - Liu, Hui

AU - Goldman, Matthew D.

AU - Whitmire, Jeannette M.

AU - Ådén, Jörgen

AU - Younson, Justine

AU - Kelly, Charles G.

AU - Gilman, Robert H.

AU - Chowdhury, Abhijit

AU - Mukhopadhyay, Asish K.

AU - Nair, G. Balakrish

AU - Papadakos, Konstantinos S.

AU - Martinez-Gonzalez, Beatriz

AU - Sgouras, Dionyssios N.

AU - Engstrand, Lars

AU - Unemo, Magnus

AU - Danielsson, Dan

AU - Suerbaum, Sebastian

AU - Oscarson, Stefan

AU - Morozova-Roche, Ludmilla A.

AU - Olofsson, Anders

AU - Gröbner, Gerhard

AU - Holgersson, Jan

AU - Esberg, Anders

AU - Strömberg, Nicklas

AU - Landström, Maréne

AU - Eldridge, Angela M.

AU - Chromy, Brett A.

AU - Hansen, Lori M.

AU - Solnick, Jay V.

AU - Lindén, Sara K.

AU - Haas, Rainer

AU - Dubois, Andre

AU - Merrell, D. Scott

AU - Schedin, Staffan

AU - Remaut, Han

AU - Arnqvist, Anna

AU - Berg, Douglas E.

AU - Borén, Thomas

PY - 2017/3/8

Y1 - 2017/3/8

N2 - 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.

AB - 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.

KW - Helicobacter pylori

KW - acid responsiveness

KW - adaptation

KW - blood group antigen-binding adhesion

KW - diversity

KW - gastric acidity

KW - gastric cancer

KW - multimerization

KW - polymorphism

KW - subpopulations

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AN - SCOPUS:85014795847

SN - 1931-3128

VL - 21

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JO - Cell Host and Microbe

JF - Cell Host and Microbe

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ER -

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

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