title: Staphylococcus aureus β-toxin production is common in strains with the β-toxin gene inactivated by bacteriophage.
abstract: 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.
authors.affiliation: Department of Microbiology, University of Iowa Carver College of Medicine, Iowa City.
authors.forename: Wilmara
authors.initials: W
authors.lastname: Salgado-Pabón
authors.affiliation: Department of Microbiology, University of Iowa Carver College of Medicine, Iowa City.
authors.forename: Alfa
authors.initials: A
authors.lastname: Herrera
authors.affiliation: Department of Microbiology, University of Iowa Carver College of Medicine, Iowa City.
authors.forename: Bao G
authors.initials: BG
authors.lastname: Vu
authors.affiliation: Department of Microbiology, University of Iowa Carver College of Medicine, Iowa City.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Stach
authors.affiliation: Department of Microbiology, University of Iowa Carver College of Medicine, Iowa City.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Merriman
authors.affiliation: Department of Microbiology, University of Iowa Carver College of Medicine, Iowa City.
authors.forename: Adam R
authors.initials: AR
authors.lastname: Spaulding
authors.affiliation: Department of Microbiology, University of Iowa Carver College of Medicine, Iowa City.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Schlievert
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000235:genetics; D004195:Disease Models, Animal; D004697:Endocarditis, Bacterial / Q000382:microbiology / Q000473:pathology; D020868:Gene Silencing; D006460:Hemolysin Proteins / Q000235:genetics / Q000378:metabolism*; D016254:Mutagenesis, Insertional; D011023:Pneumonia, Staphylococcal / Q000382:microbiology / Q000473:pathology; D039002:Prophages / Q000235:genetics*; D011817:Rabbits; D011995:Recombination, Genetic; D018805:Sepsis / Q000382:microbiology / Q000473:pathology; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics / Q000378:metabolism*; D013204:Staphylococcus Phages / Q000235:genetics*; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism* / Q000821:virology*
chemical_list: D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D013108:Sphingomyelin Phosphodiesterase; C029878:hlb protein, Staphylococcus aureus
keywords: Staphylococcus aureus; bacteriophage; infective endocarditis; pneumonia; sepsis; β-toxin