Host-dependent Lewis (Le) antigen expression in Helicobacter pylori cells recovered from Leb-transgenic mice

Abstract

Variation of surface antigen expression is a mechanism used by microbes to adapt to and persist within their host habitats. Helicobacter pylori, a persistent bacterial colonizer of the human stomach, can alter its surface Lewis (Le) antigen expression. We examined H. pylori colonization in mice to test the hypothesis that host phenotype selects for H. pylori (Le) phenotypes. When wild-type and Leb-expressing transgenic FVB/N mice were challenged with H. pylori strain HP1, expressing Lex and Ley, we found that bacterial populations recovered after 8 mo from Leb-transgenic, but not wild-type, mice expressed Leb. Changes in Le phenotype were linked to variation of a putative galactosyltransferase gene (β-(1,3)galT); mutagenesis and complementation revealed its essential role in type I antigen expression. These studies indicate that H. pylori evolves to resemble the host's gastric Le phenotype, and reveal a bacterial genetic locus that is subject to host-driven selection pressure.

Clinical Relevance and Diversity of Two Homologous Genes Encoding Glycosyltransferases in Helicobacter pylori

“…Among the strains analyzed, the jhp0562 gene had a constant length of 999 bp, except for two cases with lengths of 993 and 1,002 bp, and the corresponding ORF was always in frame. The ␤-(1,3)GalT gene presented a variable length (from 1,230 to 1,409 bp) due to a variation in the number of 21-nt tandem-repeat previously reported sequences (31)(32)(33), and 16 of the 26 (61.5%) sequences analyzed were out of frame, due to the presence of homopolymeric tract of C repeats (ranging from 8 to 15) in the middle region of the gene, resulting in a nonsense frameshift mutation (31). Interestingly, in the 13 strains in which the ␤-(1,3)GalT gene was present alone, 9 ORFs (69.2%) were in frame, whereas among the 13 isolates positive for both genes, 12 (92.3%) carried an out of frame ␤-(1,3)GalT gene.…”

“…This gene encodes a glycosyltransferase involved in the synthesis of the chemical structure of the lipopolysaccharide (LPS). It is present in the genome of the J99 strain but absent in the 26695 strain and located immediately upstream of the ␤-(1,3)-galactosyltransferase [␤- (1,3)GalT] gene (jhp0563 or HP0619 according to the annotation of these strains), which in turn encodes a ␤-(1,3)GalT involved in type I Lewis (Le) antigen (Le a and Le b ) synthesis of the LPS (3,31). jhp0562 and the ␤-(1,3)GalT gene are highly similar (Ͼ80%), especially at their 5Ј and 3Ј ends (2,9).…”

Colonize, evade, flourish

“…4A). 33,34 Next, the β(1,3)-GlcNAcT adds a second GlcNAc residue to the growing chain. 35 From there, alternating monomeric sugar additions by the GalTs and GlcNAcT build the full O-antigen backbone.…”

“…38 5 In addition, the fucosyltransferase and β(1,3) GalT genes are subject to phase variation, or random switching on and off of expression during the lifetime of a given bacterial cell. 34,39 This leads to an expansive diversity of possible Le antigen patterns across a population of H. pylori cells during the course of infection. Phase variation in the unique ability of H. pylori to produce Le antigens affords the bacterium a number of advantages inside the host.…”

“…For example, endopeptidases cleave cross-links between PG fragments; carboxypeptidases trim since the host is unlikely to react to self-epitopes. 34 Interestingly, the β(1,3) GalT gene can recombine with its upstream neighbor to create a chimeric product required for synthesis of all Lewis antigens. This suggests a novel finding that cross-talk may exist between type 1 and type 2 antigen synthesis pathways in the form of a recombined type 1 enzyme.…”