CagA of Helicobacter pylori alters the expression and cellular distribution of host proteins involved in cell signaling.
To expand our knowledge of Helicobacter pylori virulence mechanisms, we used iTRAQ (isobaric tagging reagents for relative and absolute quantification)-based proteomic analysis to investigate the effect of H. pylori on gastric AGS tissue culture cells. In particular, we were interested in finding out which effects of H. pylori were dependent on the cytotoxins CagA and VacA. Protein analysis was restricted to detergent-resistant membranes (DRMs), because both toxins were described previously to localize in lipid raft-like domains. Using H. pylori wild type and two isogenic mutants, DeltacagA and DeltavacA, we identified a total of 21 proteins that were either increased or decreased in the DRMs due to bacterial infection. The effect on three of these proteins, ezrin, syndecan-4 and Rab11-FIP1, were furthermore dependent on CagA. Because these proteins have been implicated in cell migration, adhesion and polarity, they might act as important mediators of CagA cytotoxicity.
Zeaiter
Zaher
Z
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada.
Huynh
Hien Q
HQ
Kanyo
Richard
R
Stein
Markus
M
D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology / Q000382:microbiology*; D005786:Gene Expression Regulation; D016480:Helicobacter pylori / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D021962:Membrane Microdomains / Q000382:microbiology; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D015398:Signal Transduction; D053671:Syndecan-4 / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000099149:Ezrin; D000099193:rab11 GTP-Binding Proteins
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D003598:Cytoskeletal Proteins; D011506:Proteins; D053671:Syndecan-4; D020691:rab GTP-Binding Proteins; D000099149:Ezrin; D000099193:rab11 GTP-Binding Proteins; C080866:cagA protein, Helicobacter pylori