Helicobacter pylori lipopolysaccharide interacts with TFF1 in a pH-dependent manner.
OBJECTIVE
Little is known about how bacteria establish chronic infections of mucosal surfaces. Helicobacter pylori (H. pylori), a chronic pathogen that lives in the gastric mucosa of humans, interacts with the trefoil factor family (TFF) protein TFF1, which is found in gastric mucus. We aimed to characterize the interaction of H. pylori with TFF1 and to assess the role of this interaction in mediating colonization.


METHODS
Subcellular fractions of H. pylori were immobilized and then probed with TFF1, TFF2, or TFF3. The effect of glycosidases and preincubation with monosaccharides on the interaction and binding of TFF1 to a H. pylori adhesin was assessed. The interaction between H. pylori adhesin and TFF1 was characterized using surface plasmon resonance, flow cytometry, nondenaturing polyacrylamide gel electrophoresis, coimmunofluoresence, and incubation with tissue sections.


RESULTS
The H. pylori core oligosaccharide portion (rough form) of lipopolysaccharide (RF-LPS) bound to TFF1 and to a lesser extent TFF3; this interaction was inhibited by incubation of RF-LPS with mannosidase, glucosidase, or mixed monosaccharides. TFF1 also bound to human serum albumin-conjugated mannose and glucose. The optimum pH for binding was 5.0-6.0 for TFF1 and 7.0 for TFF3. H. pylori bound TFF1 in gastric mucus ex vivo; binding of LPS-coated latex beads to human antral gastric tissue was inhibited by TFF1.


CONCLUSIONS
TFF1 interacts specifically with H. pylori RF-LPS. The pH dependence of this interaction indicates that binding of H. pylori to TFF1 in the stomach could promote colonization of the mucus layer adjacent to the gastric epithelial surface.
Reeves
Emer P
EP
University College Dublin School of Medicine and Medical Science, The Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland.
Ali
Tehmeena
T
Leonard
Paul
P
Hearty
Stephen
S
O'Kennedy
Richard
R
May
Felicity E B
FE
Westley
Bruce R
BR
Josenhans
Christine
C
Rust
Melanie
M
Suerbaum
Sebastian
S
Smith
Angeline
A
Drumm
Brendan
B
Clyne
Marguerite
M
D001422:Bacterial Adhesion / Q000502:physiology; D002648:Child; D015169:Colony Count, Microbial; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D016481:Helicobacter Infections / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008070:Lipopolysaccharides / Q000378:metabolism*; D000071163:Trefoil Factor-1; D000071164:Trefoil Factor-2; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D008070:Lipopolysaccharides; C051838:TFF1 protein, human; C000604007:TFF2 protein, human; D000071163:Trefoil Factor-1; D000071164:Trefoil Factor-2; D025521:Tumor Suppressor Proteins; C442865:lipopolysaccharide, Helicobacter pylori