Staphylococcus aureus β-toxin production is common in strains with the β-toxin gene inactivated by bacteriophage

J Infect Dis. 2014 Sep 1;210(5):784-92. doi: 10.1093/infdis/jiu146. Epub 2014 Mar 11.


Background: Staphylococcus aureus causes life-threatening infections, including infective endocarditis, sepsis, and pneumonia. β-toxin is a sphingomyelinase encoded for by virtually all S. aureus strains and exhibits human immune cell cytotoxicity. The toxin enhances S. aureus phenol-soluble modulin activity, and its activity is enhanced by superantigens. The bacteriophage φSa3 inserts into the β-toxin gene in human strains, inactivating it in the majority of S. aureus clonal groups. Hence, most strains are reported not to secrete β-toxin.

Methods: This dynamic was investigated by examining β-toxin production by multiple clonal groups of S. aureus, both in vitro and in vivo during infections in rabbit models of infective endocarditis, sepsis, and pneumonia.

Results: β-toxin phenotypic variants are common among strains containing φSa3. In vivo, φSa3 is differentially induced in heart vegetations, kidney abscesses, and ischemic liver compared to spleen and blood, and in vitro growth in liquid culture. Furthermore, in pneumonia, wild-type β-toxin production leads to development of large caseous lesions, and in infective endocarditis, increases the size of pathognomonic vegetations.

Conclusions: This study demonstrates the dynamic interaction between S. aureus and the infected host, where φSa3 serves as a regulator of virulence gene expression, and increased fitness and virulence in new environments.

Keywords: Staphylococcus aureus; bacteriophage; infective endocarditis; pneumonia; sepsis; β-toxin.

Publication types

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

MeSH terms

  • Animals
  • Bacterial Toxins / genetics
  • Disease Models, Animal
  • Endocarditis, Bacterial / microbiology
  • Endocarditis, Bacterial / pathology
  • Gene Silencing*
  • Hemolysin Proteins / genetics
  • Hemolysin Proteins / metabolism*
  • Mutagenesis, Insertional
  • Pneumonia, Staphylococcal / microbiology
  • Pneumonia, Staphylococcal / pathology
  • Prophages / genetics*
  • Rabbits
  • Recombination, Genetic
  • Sepsis / microbiology
  • Sepsis / pathology
  • Sphingomyelin Phosphodiesterase / genetics
  • Sphingomyelin Phosphodiesterase / metabolism*
  • Staphylococcus Phages / genetics*
  • Staphylococcus aureus / genetics
  • Staphylococcus aureus / metabolism*
  • Staphylococcus aureus / virology*


  • Bacterial Toxins
  • Hemolysin Proteins
  • Sphingomyelin Phosphodiesterase
  • hlb protein, Staphylococcus aureus