Helicobacter pylori Strains from Duodenal Ulcer Patients Exhibit Mixed babA/B Genotypes with Low Levels of BabA Adhesin and Lewis b Binding

Abstract

Here, we show higher prevalence of mixed babA/B genotypes among BabA-low/Le(b)-low clinical strains. Recombination of babA and babB genes across their loci may yield lower BabA expression and lower Le(b) binding activity. We conclude that H. pylori strains with lower Le(b) binding activity are better adapted for colonization of the gastric metaplastic patches in the duodenum and enhance the risk of duodenal ulcers.

Helicobacter pyloriBabA in adaptation for gastric colonization

“…The reported prevalence of H. pylori containing babA shows great variation across different parts of the world[28,32,42-55] as shown in Table 2. However, we previously reported the BabA expression level by immunoblotting and Leb binding in diverse collection of H. pylori strains and divided in to high, low, and non BabA expressing strains[52].…”

“…We detected that the strains expressing low levels (less than 10% to that of J99) of BabA protein did not mediate the enough Leb binding activity whereas, the strains expressing high level (more than 20% to that of J99) of BabA did enough Leb binding[52]. However, Saberi et al[42] categorized the H. pylori strains in four types depending on the BabA expression and Leb-binding, strains expressing high level BabA showed high Leb-binding, strains expressing low level BabA showed low Leb-binding whereas strains with no BabA expression showed no Leb-binding (8%) as well as low Leb-binding (30%) activity.…”

“…Furthermore, the triple-positive (BabA, CagA and vacA s1-positive) strains of H. pylori shows greater colonization densities, elevated levels of gastric inflammation and a higher incidence of intestinal metaplasia in patients in contrast with the only CagA and vacA s1 positive strains[101,41]. Despite of the association of high level BabA with severe clinical outcomes, surprisingly, it has been also found that low level BabA expressing strains could more likely be associated with increased mucosal inflammation and severe clinical outcomes compared to that of high level BabA-positive and Leb binding strains[42,52]. Although, the underlying mechanisms remains unclear, it has been hypothesized that during adulthood, the induced hyperacidity may enhance the development of gastric metaplastic patches in the duodenum and the H. pylori expressing low levels of BabA and Leb attachment are able to detach from the gastric niche and reattached to the gastric metaplastic patches in the duodenum and develop the ulcers at the gastric-duodenal tissue border[42].…”

“…Despite of the association of high level BabA with severe clinical outcomes, surprisingly, it has been also found that low level BabA expressing strains could more likely be associated with increased mucosal inflammation and severe clinical outcomes compared to that of high level BabA-positive and Leb binding strains[42,52]. Although, the underlying mechanisms remains unclear, it has been hypothesized that during adulthood, the induced hyperacidity may enhance the development of gastric metaplastic patches in the duodenum and the H. pylori expressing low levels of BabA and Leb attachment are able to detach from the gastric niche and reattached to the gastric metaplastic patches in the duodenum and develop the ulcers at the gastric-duodenal tissue border[42]. The BabA adhesin expression also seems tightly associated with the onset of type 4 secretory system (T4SS)-related host response in vivo [100].…”

Dynamic Expression of the BabA Adhesin and Its BabB Paralog during Helicobacter pylori Infection in Rhesus Macaques

“…Sequence analysis of diverse clinical isolates demonstrates that indeed there appears to be frequent DNA shuffling between babA and babB and, to a lesser extent, babC (18)(19)(20). Dinucleotide repeats in the 5= coding region of babA, babB, and other OMPs could also promote on-off phase variation by slipped-strand mispairing during DNA replication (21,22), which further contributes to the potential for variable BabA expression.…”