Novel Helicobacter pylori α1,2-fucosyltransferase, a key enzyme in the synthesis of Lewis antigens

Wang, Ge; Boulton, P; Chan, Nora W. C.; Palcic, Monica M.; Taylor, Diane E.

doi:10.1099/00221287-145-11-3245

Cited by 101 publications

(89 citation statements)

References 31 publications

(38 reference statements)

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“…The products of these genes have different fine specificities (5). For this reason, the homologues of HP0379 and HP0651 are designated futA and futB, respectively; ␣2-fucT (the homologue of gene HP093-HP094 in strain 26695) is designated futC (21,22). A ␤4-galT gene has recently been identified in H. pylori (the homologue of HP0826 in strain 26695 [14]).…”

mentioning

confidence: 99%

Phase Variation in H Type I and Lewis a Epitopes of Helicobacter pylori Lipopolysaccharide

Appelmelk

Martino²,

Veenhof

et al. 2000

Infect Immun

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Helicobacter pylori NCTC 11637 lipopolysaccharide (LPS) expresses the human blood group antigens Lewis x (Lex), Ley, and H type I. In this report, we demonstrate that the H type I epitope displays high-frequency phase variation. One variant expressed Lex and Ley and no H type I as determined by serology; this switch was reversible. Insertional mutagenesis in NCTC 11637 of JHP563 (a poly(C) tract containing an open reading frame homologous to glycosyltransferases) yielded a transformant with a serotype similar to the phase variant. Structural analysis of the NCTC 11637 LPS confirmed the loss of the H type I epitope. Sequencing of JHP563 in strains NCTC 11637, an H type I-negative variant, and an H type I-positive switchback variant showed a C14 (gene on), C13 (gene off), and C14 tract, respectively. Inactivation of strain G27, which expresses Lex, Ley, H type I, and Lea, yielded a transformant that expressed Lex and Ley. We conclude that JHP563 encodes a β3-galactosyltransferase involved in the biosynthesis of H type I and Lea and that phase variation in H type I is due to C-tract changes in this gene. A second H type I-negative variant (variant 3a) expressed Lex and Lea and had lost both H type I and Leyexpression. Inactivation of HP093-HP094 resulted in a transformant expressing Lex and lacking Ley and H type I. Structural analysis of a mutant LPS confirmed the serological data. We conclude that the HP093-HP094 α2-fucosyltransferase (α2-FucT) gene product is involved in the biosynthesis of both Ley and Lex. Finally, we inactivated HP0379 in strain 3a. The transformant had lost both Lex and Leaexpression, which demonstrates that the HP0379 gene product is both an α3- and an α4-FucT. Our data provide understanding at the molecular level of how H. pylori is able to diversify in the host, a requirement likely essential for successful colonization and transmission.

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confidence: 99%

Phase Variation in H Type I and Lewis a Epitopes of Helicobacter pylori Lipopolysaccharide

Appelmelk

Martino²,

Veenhof

et al. 2000

Infect Immun

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“…The completion of the genome sequence of two strains (1, 51) facilitated the annotation of 22 putative LPS glycosyltransferase genes based on homologies to LPS genes from other organisms, but only 4 of these have been functionally characterized. These include three fucosyltransferases which are involved in expression of Lewis antigens (31,41,55). In addition, Logan and coworkers (29) used functional genomics to identify and conclusively show that the HP0826 gene encoded the ␤-1,4-galactosyltransferase which was critical in O-chain backbone biosynthesis.…”

Section: Discussionmentioning

confidence: 99%

Identification of a d - glycero - d - manno -Heptosyltransferase Gene from Helicobacter pylori

et al. 2005

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“…The molecular basis of O-antigen phase variation has been attributed to four genes, futC, which encodes an AE-1,2-fucosyltransferase (Wang et al, 1999), galT, which encodes a â-1,3-galactosyltransferase , and futA and futB, which encode AE-1,3-fucosyltransferases of differing fine specificity (Appelmelk et al, 1999;Ge et al, 1997;Martin et al, 1997). All four genes contain a homopolymeric tract of dC within the 59 end of their ORFs.…”

Section: Introductionmentioning

confidence: 99%

Analysis of the role of HP0208, a phase-variable open reading frame, and its homologues HP1416 and HP0159 in the biosynthesis of Helicobacter pylori lipopolysaccharide

Langdon

Craig

Goldrick

et al. 2005

Journal of Medical Microbiology

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The roles of the three ORFs HP0208, HP0159 and HP1416 in the biosynthesis of Helicobacter pylori 26695 LPS were investigated in this study. These ORFs represent a paralogous family of genes with homology to the Salmonella enterica serovar Typhimurium (hereafter referred to as S. typhimurium) waaJ gene, which encodes an AE-1,2-glycosyltransferase required for core LPS biosynthesis. HP0208 contains multiple tandem repeats of the dimer 59GA at its 59 end and its expression is predicted to be subject to phase variation. The number of 59GA repeats present in this ORF was found to be non-permissive for the expression of HP0208 in the majority of H. pylori strains examined. To determine a role for this ORF in LPS biosynthesis a non-phase-variable, constitutively expressed variant of HP0208 was constructed and introduced into the genome of H. pylori 26695. Analysis of the LPS profile of this strain by Tricine-SDS-PAGE and immunoblotting with anti-Lewis Y antigen (Le y ) mAbs confirmed a role for HP0208 in the biosynthesis of core LPS. A role for HP0159 and HP1416 in the biosynthesis of core LPS was also established. Although homologous to waaJ, H. pylori HP0208, HP0159 and HP1416 failed to complement an S. typhimurium waaJ mutant, suggesting that these ORFs encode functionally different enzymes.

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Novel Helicobacter pylori α1,2-fucosyltransferase, a key enzyme in the synthesis of Lewis antigens

Cited by 101 publications

References 31 publications

Phase Variation in H Type I and Lewis a Epitopes of Helicobacter pylori Lipopolysaccharide

Phase Variation in H Type I and Lewis a Epitopes of Helicobacter pylori Lipopolysaccharide

Identification of a d - glycero - d - manno -Heptosyltransferase Gene from Helicobacter pylori

Analysis of the role of HP0208, a phase-variable open reading frame, and its homologues HP1416 and HP0159 in the biosynthesis of Helicobacter pylori lipopolysaccharide

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