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 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, *
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.
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Submitted on : Friday, July 26, 2019 - 4:03:58 PM
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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, Elsevier, 2017, 21 (3), pp.376-389. ⟨10.1016/j.chom.2017.02.013⟩. ⟨pasteur-02195957⟩

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