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

Abstract

Heterogeneity amongbabA genes, babA1 (silent) and babA2 (expressed). We found that a babA2-cam derivative of strain 17875 regained Leb binding by recombination of the formerly silent babA1 gene into the expressed and partially homologous babB locus. The chimeric BabB͞A adhesin binds Leb with an affinity similar to that of wild-type BabA adhesin, but its expression level was lower and was subject to phase variation through slipped-strand mispairing. Equivalent results were obtained with strain NCTC11638. We propose that adhesin metastability and heterogeneity contributes to bacterial fitness and results in some clones having potential for periodic activation and deactivation of virulence appropriate for intensity of the host response to infection.

Helicobacter pylori BabA Expression, Gastric Mucosal Injury, and Clinical Outcome

“…However, we were unable to confirm any relationship between the number of adenine residues within the −10 to −35 region and BabA status ( Figure 4). Although previous reports have suggested that chimeric babA/B or babB/A points were located close to the start codon, 24,25 we did not detect any chimeric formation within the region 600 bp from the start codon (data not shown).…”

“…24,25 This region is stable when the number of adenines was 14, but would become nonfunctional when the number was reduced to 10. 24 The number of adenine residues was 8 -14 in the strains we analyzed. However, we were unable to confirm any relationship between the number of adenine residues within the −10 to −35 region and BabA status ( Figure 4).…”

“…For example, H pylori strains unable to bind to Lewis b antigen (Le b ) have been reported to contain signal peptide sequences that are identical to those of strains with a functional babA2 gene (eg, strain 26695). 23 It also has been suggested that babA expression may be regulated transcriptionally 24 and that there are chimeric babAbabB genes (chimera babA/B or babB/A). 24,25 Finally, not all of these PCR-based studies have shown an association between babA2 and intense cellular mucosal inflammations and/ or increased risk of peptic ulcer diseases and gastric cancer (Table 1).…”

“…23 It also has been suggested that babA expression may be regulated transcriptionally 24 and that there are chimeric babAbabB genes (chimera babA/B or babB/A). 24,25 Finally, not all of these PCR-based studies have shown an association between babA2 and intense cellular mucosal inflammations and/ or increased risk of peptic ulcer diseases and gastric cancer (Table 1). [10][11][12][13]19,20,22 Therefore, in the current study, we have compared results from PCR-based strategies that currently are used to predict BabA functional status with those from strategies that measure actual babA expression (ie, immunoblotting) and Le b binding.…”

Inflammation, atrophy, and gastric cancer

“…Adherence of H. pylori to the gastric epithelium is a complicated process that involves a number of bacterial cell-surface receptors, including the Lewis B-bind- ing (Le b -binding) adhesin BabA (34), an outer membrane protein encoded by babA2 that binds the histo-blood group antigen Le b on the surface of epithelial cells. Even H. pylori strains that do not bind Le b usually possess silent babA gene sequences that can be activated by recombination events (35). Infection with H. pylori strains containing babA2, cagA, and the vacuolating cytotoxin (Vac) allele vacAS1 confers the highest risk of gastric cancer (36).…”