Functional Adaptation of BabA, the H. pylori ABO Blood Group Antigen Binding Adhesin

Abstract

Adherence by Helicobacter pylori increases the risk of gastric disease. Here, we report that more than 95% of strains that bind fucosylated blood group antigen bind A, B, and O antigens (generalists), whereas 60% of adherent South American Amerindian strains bind blood group O antigens best (specialists). This specialization coincides with the unique predominance of blood group O in these Amerindians. Strains differed about 1500-fold in binding affinities, and diversifying selection was evident in babA sequences. We propose that cycles of selection for increased and decreased bacterial adherence contribute to babA diversity and that these cycles have led to gradual replacement of generalist binding by specialist binding in blood group O-dominant human populations.

Metastability of Helicobacter pylori bab adhesin genes and dynamics in Lewis b antigen binding

“…For Scatchard analysis, binding affinity and capacity were determined as described in ref. 3. Biotinylation of Leb-APD-HSA (Isosep, Tullinge, Sweden) was performed as described in ref.…”

“…For example, reference strain CCUG17875 (here denoted 17875) has two babA genes: babA2, from which the BabA adhesin is expressed, and babA1, which is silent because of an incomplete signal peptide (5). The babB gene is highly homologous to babA at its 5Ј and 3Ј ends but not at the central region that (in babA) determines the specificity of receptor binding (3,5,19). Other hop genes, babB included, contain repetitive sequence motifs that are prone to frameshift mutation and thereby metastable hop gene expression (17,18,20).…”

“…Functional receptors for H. pylori adherence include fucosylated ABO blood group antigens (2, 3) and sialyl-Lewis x͞a antigens (4). These receptors are recognized by the blood group antigen-binding adhesin BabA, which binds Lewis b antigen (Leb) and related ABO antigens (3,5), and the sialic acid-binding adhesin, SabA (4). To date, BabA-Leb is the best-characterized of H. pylori's several adhesin-receptor interactions (3,(5)(6)(7).…”

In VitroandIn VivoAntibacterial Activities of Patchouli Alcohol, a Naturally Occurring Tricyclic Sesquiterpene, against Helicobacter pylori Infection

“…To avoid gastric acid and search for a suitable proliferation environment, the flagella of H. pylori, consisting of FlaA and FlaB proteins, provide strong motility to penetrate gastric mucus (6,7). During this process, some adhesive proteins from the H. pylori membrane are affected and form a strong attachment to gastric epithelial cells (8). Outer membrane proteins, including blood group antigen-binding adhesion (BabA), adherence-associated lipoprotein A (AlpA), and adherence-associated lipoprotein B (AlpB), reportedly contribute to this process (9).…”

Expression, purification and X-ray crystallographic analysis of theHelicobacter pyloriblood group antigen-binding adhesin BabA

“…Along with the secreted virulence factors CagA and VacA, another important virulence trait of H. pylori is the ability to strongly adhere to the gastric mucosa. The blood group antigen-binding adhesin (BabA) is a major adhesin that interacts with fucosylated Lewis b (Le b ) and H type 1 blood group antigens on the surface of human gastric epithelial cells (Boré n et al, 1993;Aspholm-Hurtig et al, 2004;Moore et al, 2011). The reference strain CCUG17875 possesses two babA genes: a silent babA1 locus and a babA2 gene that is expressed as functional BabA adhesin (Ilver et al, 1998).…”