Global regulation of virulence and the stress response by CsrA in the highly adapted human gastric pathogen Helicobacter pylori

Mol Microbiol. 2004 Jan;51(1):15-32. doi: 10.1046/j.1365-2958.2003.03788.x.


Although successful and persistent colonization of the gastric mucosa depends on the ability to respond to changing environmental conditions and co-ordinate the expression of virulence factors during the course of infection, Helicobacter pylori possesses relatively few transcriptional regulators. We therefore investigated the contribution of the regulatory protein CsrA to global gene regulation in this important human pathogen. CsrA was necessary for full motility and survival of H. pylori under conditions of oxidative stress. Loss of csrA expression deregulated the oxidant-induced transcriptional responses of napA and ahpC, the acid induction of napA, cagA, vacA, the urease operon, and fur, as well as the heat shock responses of napA, groESL and hspR. Although the level of napA transcript was higher in the csrA mutant, its stability was similar in the wild-type and mutant strains, and less NapA protein was produced in the mutant strain. Finally, H. pylori strains deficient in the production of CsrA were significantly attenuated for virulence in a mouse model of infection. This work provides evidence that CsrA has a broad role in regulating the physiology of H. pylori in response to environmental stimuli, and may be important in facilitating adaptation to the different environments encountered during colonization of the gastric mucosa. Furthermore, CsrA appears to mediate its effects in H. pylori at the post-transcriptional level by influencing the processing and translation of target transcripts, with minimal effect on the stability of the target mRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / genetics
  • Base Sequence
  • Cloning, Molecular
  • DNA Damage
  • DNA Primers
  • DNA, Bacterial / genetics
  • Escherichia coli / genetics
  • Gastric Mucosa / microbiology*
  • Gene Expression Regulation, Bacterial
  • Genetic Complementation Test
  • Helicobacter pylori / genetics*
  • Helicobacter pylori / isolation & purification
  • Helicobacter pylori / pathogenicity*
  • Humans
  • Mutagenesis, Site-Directed
  • Transcription Factors / genetics*
  • Transcription, Genetic
  • Virulence / genetics*


  • Bacterial Proteins
  • CsrA protein, Helicobacter pylori
  • DNA Primers
  • DNA, Bacterial
  • Transcription Factors