CagA tyrosine phosphorylation and interleukin-8 induction by Helicobacter pylori are independent from alpAB, HopZ and bab group outer membrane proteins.
In several studies Helicobacter pylori type I strains (cag-positive strains) have been described to translocate their CagA protein into epithelial cells, where it is tyrosine-phosphorylated. The intimate contact allows a Cag-dependent bacteria-to-cell signaling inducing the secretion of the chemokine interleukin-8. Although a contact between the bacterial and the eukaryotic cell is known to be necessary for these signal transduction events the bacterial adhesin and the cellular receptor are unknown, so far. In this study, we investigated the influence of several outer membrane proteins associated with adherence on CagA translocation and IL-8 induction. The quantitative assessment of a cag deletion mutant strain binding to epithelial cells revealed that the Cag secretion apparatus is not primarily necessary for attachment. In contrast, the knockout mutation of the adherence-associated alpAB locus significantly reduced the binding capacity in two independent strains. Despite this partial adherence defect, the alpAB mutation did not affect CagA translocation and IL-8 induction. The mutagenesis of the bab group genes hp317, hp896 and hp1243 in H. pylori 26695 did not influence the Cag-dependent signaling either. No causative linkage could be found between the production of the outer membrane proteins HopZ, OipA or seven additional outer membrane proteins and CagA translocation or IL-8 induction.
Odenbreit
Stefan
S
Max von Pettenkofer Institut für Hygiene und Medizinische Mikrobiologie, Ludwig Maximilians Universität München, Germany. odenbreit@m3401.mpk.med.uni-muenchen.de
Kavermann
Holger
H
Püls
Jürgen
J
Haas
Rainer
R
D018829:Adhesins, Bacterial / Q000378:metabolism; D000942:Antigens, Bacterial; D001422:Bacterial Adhesion / Q000502:physiology; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D015153:Blotting, Western; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000378:metabolism; D016254:Mutagenesis, Insertional; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism
D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D016209:Interleukin-8; C080866:cagA protein, Helicobacter pylori; D014443:Tyrosine