Inhibition of Helicobacter pylori adherence by a peptide derived from neuraminyl lactose binding adhesin.
Helicobacterpylori, like many other gut colonizing bacteria, binds to sialic acid rich macromolecules present on the gastric epithelium. NLBH (neuraminyl lactose binding haemagglutinin) a 32 kDa adhesin located on the surface of H. pylori has been shown to have specific affinity towards NeuAcalpha2,3Galbeta1,4Gluc(3'SL). This sialic acid moiety is over-expressed in an atrophic stomach undergoing parietal cell depletion. Antibodies against a lysine rich peptide fragment of NLBH inhibit agglutination of human erythrocytes. This lysine rich sequence from NLBH was proposed to be the receptor-binding site. In order to elucidate the binding of NLBH to gastric epithelium, a peptide (D-P-K-R-T-I-Q-K-K-S) was synthesized. A series of experiments were performed involving adherence inhibition assays, 2D-NMR, molecular modelling and measurement of modulation in acid secretion. Results indicated that the peptide fragment could be involved in receptor recognition, which is important for the binding of H. pylori to gastric epithelium. The binding is possibly through hydrogen bonding. Two lysines and a threonine residue seem to be within the hydrogen bonding distance of NeuAcalpha2,3Galbeta1,4Gluc. Further, in vitro assays were performed to evaluate the role of the peptide on acid secretion by parietal cells isolated from human fundal biopsies. Interestingly, the peptide increases acid secretion only in H. pylori negative and in treated patients but not in H. pylori positive patients. This highlights the role of NLBH in acid secretion and could be of some consequence in the prognosis of the disease.
Chaturvedi
G
G
Department of Microbiology, Panjab University, Chandigarh, India.
Tewari
R
R
Mrigank
Agnihotri
N
N
Vishwakarma
R A
RA
Ganguly
N K
NK
D000818:Animals; D001422:Bacterial Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism*; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D007785:Lactose / Q000031:analogs & derivatives* / Q000737:chemistry*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D010295:Parietal Cells, Gastric / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology; D011817:Rabbits; D012794:Sialic Acids / Q000737:chemistry*
D009842:Oligopeptides; D010446:Peptide Fragments; D012794:Sialic Acids; C000020:N-acetylneuraminoyllactose; D007785:Lactose