Mutation of cytotoxin-associated gene A affects expressions of antioxidant proteins of Helicobacter pylori

World J Gastroenterol. 2009 Feb 7;15(5):599-606. doi: 10.3748/wjg.15.599.

Abstract

Aim: To determine if disruption of the cagA gene of Helicobacter pylori (H pylori) has an effect on the expression of other proteins at proteome level.

Methods: Construction of a cagA knock out mutant Hp27_Delta cagA (cagA(-)) via homologous recombination with the wild-type strain Hp27 (cagA(+)) as a recipient was performed. The method of sonication-urea-CHAPS-DTT was employed to extract bacterial proteins from both strains. Soluble proteins were analyzed by two-dimensional electrophoresis (2-DE). Images of 2-DE gels were digitalized and analyzed. Only spots that had a statistical significance in differential expression were selected and analyzed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS). Biological information was used to search protein database and identify the biological function of proteins.

Results: The proteome expressions between wild-type strain and isogenic mutant with the cagA gene knocked-out were compared. Five protein spots with high abundance in bacteria proteins of wild-type strains, down-regulated or absently expressed in bacteria proteins of mutants, were identified and analyzed. From a quantitative point of view, the identified proteins are related to the cagA gene and important antioxidant proteins of H pylori, including alkyl hydroperoxide reductase (Ahp), superoxide dismutase (SOD) and modulator of drug activity (Mda66), respectively, suggesting that cagA is important to maintain the normal activity of antioxidative stress and ensure H pylori persistent colonization in the host.

Conclusion: cagA gene is relevant to the expressions of antioxidant proteins of H pylori, which may be a novel mechanism involved in H pylori cagA pathogenesis.

MeSH terms

  • Antigens, Bacterial / genetics*
  • Antigens, Bacterial / isolation & purification
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / isolation & purification
  • Bacterial Toxins / genetics*
  • DNA Primers
  • Electrophoresis, Gel, Two-Dimensional
  • Gastritis / microbiology
  • Gastritis / pathology
  • Gene Expression Regulation, Bacterial*
  • Helicobacter pylori / genetics*
  • Humans
  • Peptide Mapping
  • Proteome / genetics*
  • Restriction Mapping
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • Bacterial Toxins
  • DNA Primers
  • Proteome
  • cagA protein, Helicobacter pylori