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Cell Host Microbe. 2017 Mar 8;21(3):376-389. doi: 10.1016/j.chom.2017.02.013.

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

Author information

1
Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden.
2
Department of Applied Physics and Electronics, Umeå University, 901 87 Umeå, Sweden.
3
Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden; School of Life Sciences, CBS, University of Nottingham, NG7 2RD Nottingham, UK.
4
Department of Medical Biochemistry and Cell Biology, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
5
Structural and Molecular Microbiology, VIB Department of Structural Biology, VIB, 1050 Brussels, Belgium; Structural Biology Brussels, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
6
Department of Pathology, Medical Institute, Sumy State University, 40007 Sumy, Ukraine.
7
Department of Chemistry, Umeå University, 901 87 Umeå, Sweden.
8
Max von Pettenkofer Institute of Hygiene and Medical Microbiology, LMU Munich, 80336 Munich, Germany.
9
Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden; Department of Medical Biosciences, Umeå University, 901 85 Umeå, Sweden.
10
Department of Odontology, Umeå University, 901 87 Umeå, Sweden.
11
Department of Medicine, USUHS, Bethesda, MD 20814, USA.
12
Department of Pediatrics, USUHS, Bethesda, MD 20814, USA.
13
Department of Microbiology and Immunology, USUHS, Bethesda, MD 20814, USA.
14
King's College London, Dental Institute, London SE1 9RT, UK.
15
Department of International Health, John Hopkins School of Public Health, Baltimore, MD 21205, USA.
16
Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education & Research, Kolkata 700020, India.
17
Division of Bacteriology, National Institute of Cholera and Enteric Diseases P33, CIT Road, Kolkata 700010, India.
18
Translational Health Science and Technology Institute 496, Phase-III, Udyog Vihar Gurgaon, 122016 Haryana, India.
19
Hellenic Pasteur Institute, Athens 11521, Greece.
20
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
21
Department of Laboratory Medicine, Microbiology, Örebro University Hospital, 701 85 Örebro, Sweden.
22
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.
23
Centre for Synthesis and Chemical Biology, School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland.
24
Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden.
25
Department of Medical Biosciences, Umeå University, 901 85 Umeå, Sweden.
26
Department of Pathology and Laboratory Medicine, University of California Davis School of Medicine, Sacramento, CA 95817, USA.
27
Departments of Medical Microbiology and Immunology, Center for Comparative Medicine, University of California Davis, Davis, CA 95616, USA.
28
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.
29
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.
30
Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
31
Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden. Electronic address: thomas.boren@umu.se.

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

PMID:
28279347
PMCID:
PMC5392239
DOI:
10.1016/j.chom.2017.02.013
[Indexed for MEDLINE]
Free PMC Article

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