Roles of Helicobacter pylori BabA in gastroduodenal pathogenesis

Abstract

Interactions between BabA and Lewis b (Le(b)) related antigens are the best characterized adhesin-receptor interactions in Helicobacter pylori (H pylori). Several mechanisms for the regulation of BabA expression are predicted, including at both transcriptional and translational levels. The formation of chimeric proteins (babA/B or babB/A chimeras) seems to play an especially important role in translational regulation. Chimeric BabB/A protein had the potential to bind Le(b); however, protein production was subject to phase variation through slipped strand mispairing. The babA gene was cloned initially from strain CCUG17875, which contains a silent babA1 gene and an expressed babA2 gene. The sequence of these two genes differs only by the presence of a 10 bp deletion in the signal peptide sequence of babA1 that eliminates its translational initiation codon. However, the babA1 type deletion was found only in strain CCUG17875. A few studies evaluated BabA status by immunoblot and confirmed that BabA-positive status in Western strains was closely associated with severe clinical outcomes. BabA-positive status also was associated with the presence of other virulence factors (e.g. cagA-positive status and vacA s1 genotype). A small class of strains produced low levels of the BabA protein and lacked Le(b) binding activity. These were more likely to be associated with increased mucosal inflammation and severe clinical outcomes than BabA-positive strains that exhibited Le(b) binding activity. The underlying mechanism is unclear, and further studies will be necessary to investigate how the complex BabA-receptor network is functionally coordinated during the interaction of H pylori with the gastric mucosa.

Figure 1

Biosynthetic pathways of Lewis antigens starting from type 1 lacto series core chains. Starting from type 1 core chains, an α1, 2-fucosyltransferase (Se) transfers fucose (Fuc) to the terminal galactose (Gal), resulting in the H-1 antigen (H1). H-1 antigen is a target for GalNAc- or Gal-transferases (in blood group A or B individuals) or remains unmodified (in blood group O individuals). These intermediates the are modified for the fucosylation step by an α1,3/4-fucosyltransferase (Le), resulting in the difucosylated histo-blood group antigens ALe^b, ALe^b and Le^b. Non-secretors are unable to produce an active Se product, and are only targets for the Le gene product Le^a.

Figure 2

Genomic location of the babA, babB, and babC genes in strains J99, 26695, and HPAG1. CT: CT dinucleotide repeats.