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.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Jeanna A
authors.initials: JA
authors.lastname: Bugaytsova
authors.affiliation: Department of Applied Physics and Electronics, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Oscar
authors.initials: O
authors.lastname: Björnham
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Yevgen A
authors.initials: YA
authors.lastname: Chernov
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Pär
authors.initials: P
authors.lastname: Gideonsson
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Henriksson
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Melissa
authors.initials: M
authors.lastname: Mendez
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Rolf
authors.initials: R
authors.lastname: Sjöström
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden; School of Life Sciences, CBS, University of Nottingham, NG7 2RD Nottingham, UK.
authors.forename: Jafar
authors.initials: J
authors.lastname: Mahdavi
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Shevtsova
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
authors.forename: Dag
authors.initials: D
authors.lastname: Ilver
authors.affiliation: Structural and Molecular Microbiology, VIB Department of Structural Biology, VIB, 1050 Brussels, Belgium; Structural Biology Brussels, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Kristof
authors.initials: K
authors.lastname: Moonens
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
authors.forename: Macarena P
authors.initials: MP
authors.lastname: Quintana-Hayashi
authors.affiliation: Department of Pathology, Medical Institute, Sumy State University, 40007 Sumy, Ukraine.
authors.forename: Roman
authors.initials: R
authors.lastname: Moskalenko
authors.affiliation: Department of Chemistry, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Christopher
authors.initials: C
authors.lastname: Aisenbrey
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Bylund
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Alexej
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Åberg
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Brännström
authors.affiliation: Max von Pettenkofer Institute of Hygiene and Medical Microbiology, LMU Munich, 80336 Munich, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Königer
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Susanne
authors.initials: S
authors.lastname: Vikström
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden; Department of Medical Biosciences, Umeå University, 901 85 Umeå, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Rakhimova
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Hofer
authors.affiliation: Department of Odontology, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Ögren
authors.affiliation: Department of Medicine, USUHS, Bethesda, MD 20814, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, USUHS, Bethesda, MD 20814, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Goldman
authors.affiliation: Department of Microbiology and Immunology, USUHS, Bethesda, MD 20814, USA.
authors.forename: Jeannette M
authors.initials: JM
authors.lastname: Whitmire
authors.affiliation: Department of Chemistry, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Jörgen
authors.initials: J
authors.lastname: Ådén
authors.affiliation: King's College London, Dental Institute, London SE1 9RT, UK.
authors.forename: Justine
authors.initials: J
authors.lastname: Younson
authors.affiliation: King's College London, Dental Institute, London SE1 9RT, UK.
authors.forename: Charles G
authors.initials: CG
authors.lastname: Kelly
authors.affiliation: Department of International Health, John Hopkins School of Public Health, Baltimore, MD 21205, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Gilman
authors.affiliation: Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education & Research, Kolkata 700020, India.
authors.forename: Abhijit
authors.initials: A
authors.lastname: Chowdhury
authors.affiliation: Division of Bacteriology, National Institute of Cholera and Enteric Diseases P33, CIT Road, Kolkata 700010, India.
authors.forename: Asish K
authors.initials: AK
authors.lastname: Mukhopadhyay
authors.affiliation: Translational Health Science and Technology Institute 496, Phase-III, Udyog Vihar Gurgaon, 122016 Haryana, India.
authors.forename: G Balakrish
authors.initials: GB
authors.lastname: Nair
authors.affiliation: Hellenic Pasteur Institute, Athens 11521, Greece.
authors.forename: Konstantinos S
authors.initials: KS
authors.lastname: Papadakos
authors.affiliation: Hellenic Pasteur Institute, Athens 11521, Greece.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Martinez-Gonzalez
authors.affiliation: Hellenic Pasteur Institute, Athens 11521, Greece.
authors.forename: Dionyssios N
authors.initials: DN
authors.lastname: Sgouras
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Engstrand
authors.affiliation: Department of Laboratory Medicine, Microbiology, Örebro University Hospital, 701 85 Örebro, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Unemo
authors.affiliation: Department of Laboratory Medicine, Microbiology, Örebro University Hospital, 701 85 Örebro, Sweden.
authors.forename: Dan
authors.initials: D
authors.lastname: Danielsson
authors.affiliation: Max von Pettenkofer Institute of Hygiene and Medical Microbiology, LMU Munich, 80336 Munich, Germany; Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, 30625 Hannover, Germany; German Center for Infection Research (DZIF), Hannover-Braunschweig Site, 30625 Hannover, Germany; German Center for Infection Research (DZIF), Munich Site, 80336 Munich, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Suerbaum
authors.affiliation: Centre for Synthesis and Chemical Biology, School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Oscarson
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Ludmilla A
authors.initials: LA
authors.lastname: Morozova-Roche
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Olofsson
authors.affiliation: Department of Chemistry, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gröbner
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Holgersson
authors.affiliation: Department of Odontology, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Esberg
authors.affiliation: Department of Odontology, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Nicklas
authors.initials: N
authors.lastname: Strömberg
authors.affiliation: Department of Medical Biosciences, Umeå University, 901 85 Umeå, Sweden.
authors.forename: Maréne
authors.initials: M
authors.lastname: Landström
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California Davis School of Medicine, Sacramento, CA 95817, USA.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Eldridge
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California Davis School of Medicine, Sacramento, CA 95817, USA.
authors.forename: Brett A
authors.initials: BA
authors.lastname: Chromy
authors.affiliation: Departments of Medical Microbiology and Immunology, Center for Comparative Medicine, University of California Davis, Davis, CA 95616, USA.
authors.forename: Lori M
authors.initials: LM
authors.lastname: Hansen
authors.affiliation: Departments of Medical Microbiology and Immunology, Center for Comparative Medicine, University of California Davis, Davis, CA 95616, USA; California National Primate Research Center, University of California Davis School of Medicine, Davis, CA 95616, USA.
authors.forename: Jay V
authors.initials: JV
authors.lastname: Solnick
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
authors.forename: Sara K
authors.initials: SK
authors.lastname: Lindén
authors.affiliation: Max von Pettenkofer Institute of Hygiene and Medical Microbiology, LMU Munich, 80336 Munich, Germany; German Center for Infection Research (DZIF), Munich Site, 80336 Munich, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Haas
authors.affiliation: Department of Medicine, USUHS, Bethesda, MD 20814, USA.
authors.forename: Andre
authors.initials: A
authors.lastname: Dubois
authors.affiliation: Department of Microbiology and Immunology, USUHS, Bethesda, MD 20814, USA.
authors.forename: D Scott
authors.initials: DS
authors.lastname: Merrell
authors.affiliation: Department of Applied Physics and Electronics, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Schedin
authors.affiliation: Structural and Molecular Microbiology, VIB Department of Structural Biology, VIB, 1050 Brussels, Belgium; Structural Biology Brussels, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Han
authors.initials: H
authors.lastname: Remaut
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Arnqvist
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Berg
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden. Electronic address: thomas.boren@umu.se.
authors.forename: Thomas
authors.initials: T
authors.lastname: Borén
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism*; D001422:Bacterial Adhesion; D005753:Gastric Mucosa / Q000382:microbiology* / Q000473:pathology; D016481:Helicobacter Infections / Q000382:microbiology* / Q000473:pathology; D016480:Helicobacter pylori / Q000502:physiology*; D006863:Hydrogen-Ion Concentration
chemical_list: D018829:Adhesins, Bacterial; C400429:BabA protein, Helicobacter pylori
keywords: Helicobacter pylori; acid responsiveness; adaptation; blood group antigen-binding adhesion; diversity; gastric acidity; gastric cancer; multimerization; polymorphism; subpopulations