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

Jeanna Bugaytsova (1) , Oscar Björnham (1) , Yevgen Chernov (1) , Pär Gideonsson (1) , Sara Henriksson (1) , Melissa Mendez (1) , Rolf Sjöström (1) , Jafar Mahdavi (1, 2) , Anna Shevtsova (1) , Dag Ilver (3) , Kristof Moonens (4, 5) , Macarena Quintana-Hayashi (3) , Roman Moskalenko (6) , Christopher Aisenbrey (1) , Göran Bylund (1) , Alexej Schmidt (1) , Anna Åberg (1) , Kristof Brännström (1) , Verena Königer (7) , Susanne Vikström (1) , Lena Rakhimova (1) , Anders Hofer (1) , Johan Ögren (1) , Hui Liu (8) , Matthew Goldman (8) , Jeannette Whitmire (8) , Jörgen Ådén (1) , Justine Younson (9) , Charles Kelly (9) , Robert H Gilman (10) , Abhijit Chowdhury (11) , Asish Mukhopadhyay (12) , G. Balakrish Nair (13) , Konstantinos Papadakos (14) , Beatriz Martinez-Gonzalez (14) , Dionyssios Sgouras (14) , Lars Engstrand (15) , Magnus Unemo (16) , Dan Danielsson (16) , Sebastian Suerbaum (7, 17, 18) , Stefan Oscarson (19) , Ludmilla Morozova-Roche (1) , Anders Olofsson (1) , Gerhard Gröbner (1) , Jan Holgersson (3) , Anders Esberg (1) , Nicklas Strömberg (1) , Maréne Landström (1) , Angela Eldridge (20) , Brett Chromy (20) , Lori Hansen (20) , Jay Solnick (20) , Sara Lindén (3) , Rainer Haas (7, 21) , André Dubois (8) , D. Scott Merrell (8) , Staffan Schedin (1) , Han Remaut (22, 5) , Anna Arnqvist (1) , Douglas Berg (23) , Thomas Borén (1)

1 Umeå University
2 School of Life Sciences
3 Sahlgrenska Academy at University of Gothenburg [Göteborg]
4 ULB - Université libre de Bruxelles
5 VIB-VUB Center for Structural Biology [Bruxelles]
6 Sumy State University
7 MVP - Max Von Pettenkofer Institute
8 USUHS - Uniformed Services University of the Health Sciences
9 King‘s College London
10 Johns Hopkins Bloomberg School of Public Health [Baltimore]
11 SDLD - School of Digestive and Liver Diseases [Kolkata]
12 National Institute of Cholera and Enteric Diseases
13 THSTI - Translational Health Science and Technology Institute [Faridabad]
14 Institut Pasteur Hellénique
15 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet
16 Örebro University Hospital [Örebro, Sweden]
17 MHH - Hannover Medical School [Hannover]
18 DZIF - German Center for Infection Research - partner site Hannover-Braunschweig
19 UCD - School of Chemistry and Chemical Biology
20 UC Davis - University of California [Davis]
21 DZIF - German Center for Infection Research, Partnersite Munich
22 ULB - Département d'Informatique [Bruxelles]
23 UC San Diego - University of California [San Diego]

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

Domains: Life Sciences [q-bio]; Microbiology and Parasitology; Bacteriology

Jeanna Bugaytsova, Oscar Björnham, Yevgen Chernov, Pär Gideonsson, Sara Henriksson, et al.. Helicobacter pylori Adapts to Chronic Infection and Gastric Disease via pH-Responsive BabA-Mediated Adherence. Cell Host and Microbe, 2017, 21 (3), pp.376-389. ⟨10.1016/j.chom.2017.02.013⟩. ⟨pasteur-02195957⟩