Bugaytsova Jeanna A, Björnham Oscar, Chernov Yevgen A, Gideonsson Pär, Henriksson Sara, Mendez Melissa, Sjöström Rolf, Mahdavi Jafar, Shevtsova Anna, Ilver Dag, Moonens Kristof, Quintana-Hayashi Macarena P, Moskalenko Roman, Aisenbrey Christopher, Bylund Göran, Schmidt Alexej, Åberg Anna, Brännström Kristoffer, Königer Verena, Vikström Susanne, Rakhimova Lena, Hofer Anders, Ögren Johan, Liu Hui, Goldman Matthew D, Whitmire Jeannette M, Ådén Jörgen, Younson Justine, Kelly Charles G, Gilman Robert H, Chowdhury Abhijit, Mukhopadhyay Asish K, Nair G Balakrish, Papadakos Konstantinos S, Martinez-Gonzalez Beatriz, Sgouras Dionyssios N, Engstrand Lars, Unemo Magnus, Danielsson Dan, Suerbaum Sebastian, Oscarson Stefan, Morozova-Roche Ludmilla A, Olofsson Anders, Gröbner Gerhard, Holgersson Jan, Esberg Anders, Strömberg Nicklas, Landström Maréne, Eldridge Angela M, Chromy Brett A, Hansen Lori M, Solnick Jay V, Lindén Sara K, Haas Rainer, Dubois Andre, Merrell D Scott, Schedin Staffan, Remaut Han, Arnqvist Anna, Berg Douglas E, Borén Thomas
Department of Medical Biochemistry and Biophysics, Umeå University, 901 87 Umeå, Sweden.
Department of Applied Physics and Electronics, Umeå University, 901 87 Umeå, Sweden.
Cell Host Microbe. 2017 Mar 8;21(3):376-389. doi: 10.1016/j.chom.2017.02.013.
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.
BabA黏附素介导幽门螺杆菌与ABO血型抗原糖基化胃黏膜的高亲和力结合。我们在此表明，BabA对酸有反应——在低pH值下结合力降低，通过酸中和可恢复。不同菌株的酸反应性不同；通常与胃内不同区域相关，并在慢性感染和疾病进展过程中演变；并且取决于BabA中的pH传感器序列以及高亲和力结合的BabA多聚体的pH可逆形成。我们提出，BabA非凡的可逆酸反应性能够实现紧密的黏膜细菌黏附，同时也能有效地从脱落到酸性杀菌腔内的上皮细胞和黏液中逃脱，并且通过与babA相关基因的突变和重组，个体差异和胃酸度随时间的变化会选择BabA结合特性的生物选择和变化。这些过程产生了不同的幽门螺杆菌亚群，其中BabA的适应性进化有助于幽门螺杆菌的持续存在和明显的胃部疾病。
