SabA is the H. pylori hemagglutinin and is polymorphic in binding to sialylated glycans.
Adherence of Helicobacter pylori to inflamed gastric mucosa is dependent on the sialic acid-binding adhesin (SabA) and cognate sialylated/fucosylated glycans on the host cell surface. By in situ hybridization, H. pylori bacteria were observed in close association with erythrocytes in capillaries and post-capillary venules of the lamina propria of gastric mucosa in both infected humans and Rhesus monkeys. In vivo adherence of H. pylori to erythrocytes may require molecular mechanisms similar to the sialic acid-dependent in vitro agglutination of erythrocytes (i.e., sialic acid-dependent hemagglutination). In this context, the SabA adhesin was identified as the sialic acid-dependent hemagglutinin based on sialidase-sensitive hemagglutination, binding assays with sialylated glycoconjugates, and analysis of a series of isogenic sabA deletion mutants. The topographic presentation of binding sites for SabA on the erythrocyte membrane was mapped to gangliosides with extended core chains. However, receptor mapping revealed that the NeuAcalpha2-3Gal-disaccharide constitutes the minimal sialylated binding epitope required for SabA binding. Furthermore, clinical isolates demonstrated polymorphism in sialyl binding and complementation analysis of sabA mutants demonstrated that polymorphism in sialyl binding is an inherent property of the SabA protein itself. Gastric inflammation is associated with periodic changes in the composition of mucosal sialylation patterns. We suggest that dynamic adaptation in sialyl-binding properties during persistent infection specializes H. pylori both for individual variation in mucosal glycosylation and tropism for local areas of inflamed and/or dysplastic tissue.
Aspholm
Marina
M
Department of Odontology, Section of Oral Microbiology, Umeå University, Umeå, Sweden.
Olfat
Farzad O
FO
Nordén
Jenny
J
Sondén
Berit
B
Lundberg
Carina
C
Sjöström
Rolf
R
Altraja
Siiri
S
Odenbreit
Stefan
S
Haas
Rainer
R
Wadström
Torkel
T
Engstrand
Lars
L
Semino-Mora
Cristina
C
Liu
Hui
H
Dubois
André
A
Teneberg
Susann
S
Arnqvist
Anna
A
Borén
Thomas
T
D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D000327:Adsorption; D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism; D001422:Bacterial Adhesion; D001665:Binding Sites; D001667:Binding, Competitive; D002196:Capillaries; D004912:Erythrocytes / Q000378:metabolism / Q000382:microbiology; D005732:Gangliosides / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply / Q000382:microbiology; D017353:Gene Deletion; D016481:Helicobacter Infections / Q000276:immunology / Q000382:microbiology; D016480:Helicobacter pylori / Q000378:metabolism / Q000502:physiology*; D006384:Hemagglutination; D006388:Hemagglutinins / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008253:Macaca mulatta; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D009844:Oligosaccharides / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism*; D000080506:Sialyl Lewis X Antigen; D014699:Venules
D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; D005732:Gangliosides; D006388:Hemagglutinins; D009844:Oligosaccharides; D011134:Polysaccharides; C500808:SabA protein, Helicobacter pylori; D000080506:Sialyl Lewis X Antigen; D019158:N-Acetylneuraminic Acid