SaeR binds a consensus sequence within virulence gene promoters to advance USA300 pathogenesis

J Infect Dis. 2010 Jan 15;201(2):241-54. doi: 10.1086/649570.


This investigation examines the role of the SaeR/S 2-component system in USA300, a prominent circulating clone of community-associated methicillin-resistant Staphylococcus aureus. Using a saeR/S isogenic deletion mutant of USA300 (USA300DeltasaeR/S) in murine models of sepsis and soft-tissue infection revealed that this sensory system is critical to pathogenesis of USA300 during both superficial and invasive infection. Oligonucleotide microarray and real-time reverse-transcriptase polymerase chain reaction identified numerous extracellular virulence genes that are down-regulated in USA300DeltasaeR/S. Unexpectedly, an up-regulation of mecA and mecR1 corresponded to increased methicillin resistance in USA300DeltasaeR/S. 5'-RACE analysis defined transcript start sites for sbi, efb, mecA, lukS-PV, hlb, SAUSA300_1975, and hla, to underscore a conserved consensus sequence within promoter regions of genes under strong SaeR/S transcriptional regulation. Electrophoretic mobility shift assay experiments illustrated direct binding of SaeR(His) to promoter regions containing the conserved consensus sequence. Collectively, the findings of this investigation demonstrate that SaeR/S directly interacts with virulence gene promoters to significantly influence USA300 pathogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / physiology
  • Community-Acquired Infections / microbiology
  • Disease Models, Animal
  • Electrophoretic Mobility Shift Assay
  • Gene Expression Profiling
  • Humans
  • Methicillin-Resistant Staphylococcus aureus / genetics*
  • Methicillin-Resistant Staphylococcus aureus / pathogenicity*
  • Mice
  • Oligonucleotide Array Sequence Analysis
  • Promoter Regions, Genetic / genetics*
  • Sequence Deletion
  • Soft Tissue Infections / microbiology
  • Transcription Factors
  • Up-Regulation
  • Virulence Factors / metabolism*


  • Bacterial Proteins
  • SaeR protein, Staphylococcus aureus
  • Transcription Factors
  • Virulence Factors