An enzymatic ruler modulates Lewis antigen glycosylation of Helicobacter pylori LPS during persistent infection.
Helicobacter pylori persistently colonizes about half the human population and contributes to the development of peptic ulcer disease and gastric cancer. This organism has evolved means to structurally alter its surface characteristics to evade innate and adaptive immune responses. H. pylori produces LPS O-antigen units that can be posttranslationally fucosylated to generate Lewis antigens, structures also found on human epithelial cells. We demonstrate an extensive diversity of Lewis x and Lewis y expression in LPS O-antigen units, occurring over time and in different regions of the human stomach. Lewis expression patterns were correlated with the on/off status of the three fucosyltransferases (FucT), FutA, FutB, and FutC, which are regulated via slipped-strand mispairing in intragenic polyC tract regions of the corresponding genes. The alpha1,3-FucT, FutA and FutB, each contain a C-terminal heptad repeat region, consisting of a variable number of DD/NLRV/INY tandem repeats. Variations in the number of heptad repeats correlated to the sizes of O-antigen polymers to become decorated by fucose residues. Our data support a molecular ruler mechanism for how H. pylori varies its LPS fucosylation pattern, where one heptad repeat in the enzyme corresponds to one N-acetyl-beta-lactosamine unit in the O-antigen polysaccharide.
Microbiology and Tumor Biology Center, Karolinska Institutet, 171 77 Stockholm, Sweden. christina.nilsson@mtc.ki.se
Christina
C
Nilsson
Anna
A
Skoglund
Anthony P
AP
Moran
Heidi
H
Annuk
Lars
L
Engstrand
Staffan
S
Normark
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics*; D019281:Dimerization; D005647:Fucosyltransferases / Q000737:chemistry / Q000235:genetics*; D006031:Glycosylation; D016481:Helicobacter Infections / Q000382:microbiology*; D016480:Helicobacter pylori / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000032:analysis / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D019081:O Antigens / Q000737:chemistry / Q000378:metabolism; D009844:Oligosaccharides / Q000032:analysis / Q000378:metabolism*; D020449:Repetitive Sequences, Amino Acid; D013270:Stomach / Q000382:microbiology
D001426:Bacterial Proteins; D007983:Lewis Blood Group Antigens; C094162:Lewis Y antigen; C494219:Lewis a oligosaccharide; D008070:Lipopolysaccharides; D019081:O Antigens; D009844:Oligosaccharides; D005647:Fucosyltransferases