A two-component system that controls the expression of pneumococcal surface antigen A (PsaA) and regulates virulence and resistance to oxidative stress in Streptococcus pneumoniae

Mol Microbiol. 2004 Mar;51(6):1661-75. doi: 10.1111/j.1365-2958.2003.03917.x.


Recent genomic-based studies have identified 13 two-component signal transduction systems (TCS) in Streptococcus pneumoniae. Bacterial TCSs are important for regulating expression of bacterial genes, including those which are important to the virulence of pathogenic bacteria. We have used virulence assays together with microarray analysis to investigate the importance of pneumococcal TCS04 in the virulence and gene regulation of this pathogen. Deletion mutants of the response regulator of TCS04, rr04, were examined in three independent pneumococcal strains representing three different pneumococcal serotypes. Analysis of the virulence of the three strains enabled us to identify a serotype-specific attenuation of virulence due to deletion of rr04. Microarray comparison of the transcriptional profiles of the wild-type strains with the rr04 mutants allowed us to determine which transcriptional changes were occurring in the rr04 mutants. Virulence-associated changes were demonstrated in the attenuated strain with significant downregulation of a previously determined virulence locus, psaB, psaC and psaA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Adhesins, Bacterial
  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / physiology
  • Blood / microbiology
  • Carrier Proteins / genetics*
  • Gene Expression Regulation, Bacterial*
  • Genes, Bacterial
  • Hydrogen Peroxide / toxicity
  • Lipoproteins / genetics*
  • Lung / microbiology
  • Membrane Proteins / genetics
  • Membrane Transport Proteins*
  • Mice
  • Molecular Sequence Data
  • Mutation
  • Oligonucleotide Array Sequence Analysis
  • Oxidative Stress / genetics*
  • Pneumococcal Infections / microbiology
  • RNA, Bacterial / genetics
  • RNA, Bacterial / isolation & purification
  • Serotyping
  • Streptococcus pneumoniae / classification
  • Streptococcus pneumoniae / genetics*
  • Streptococcus pneumoniae / pathogenicity*
  • Streptococcus pneumoniae / physiology
  • Virulence / genetics*


  • ATP-Binding Cassette Transporters
  • Adhesins, Bacterial
  • Bacterial Proteins
  • Carrier Proteins
  • Lipoproteins
  • Membrane Proteins
  • Membrane Transport Proteins
  • PsaA protein, Streptococcus
  • RNA, Bacterial
  • psaB protein, Streptococcus
  • psaC protein, Streptococcus
  • Hydrogen Peroxide