title: Virulence difference between the prototypic Schu S4 strain (A1a) and Francisella tularensis A1a, A1b, A2 and type B strains in a murine model of infection.
abstract: BACKGROUND
  The use of prototypic strains is common among laboratories studying infectious agents as it promotes consistency for data comparability among and between laboratories. Schu S4 is the prototypic virulent strain of Francisella tularensis and has been used extensively as such over the past six decades. Studies have demonstrated virulence differences among the two clinically relevant subspecies of F. tularensis, tularensis (type A) and holarctica (type B) and more recently between type A subpopulations (A1a, A1b and A2). Schu S4 belongs to the most virulent subspecies of F. tularensis, subspecies tularensis.
  
  
  METHODS
  In this study, we investigated the relative virulence of Schu S4 in comparison to A1a, A1b, A2 and type B strains using a temperature-based murine model of infection. Mice were inoculated intradermally and a hypothermic drop point was used as a surrogate for death. Survival curves and the length of temperature phases were compared for all infections. Bacterial burdens were also compared between the most virulent type A subpopulation, A1b, and Schu S4 at drop point.
  
  
  RESULTS
  Survival curve comparisons demonstrate that the Schu S4 strain used in this study resembles the virulence of type B strains, and is significantly less virulent than all other type A (A1a, A1b and A2) strains tested. Additionally, when bacterial burdens were compared between mice infected with Schu S4 or MA00-2987 (A1b) significantly higher burdens were present in the blood and spleen of mice infected with MA00-2987.
  
  
  CONCLUSIONS
  The knowledge gained from using Schu S4 as a prototypic virulent strain has unquestionably advanced the field of tularemia research. The findings of this study, however, indicate that careful consideration of F. tularensis strain selection must occur when the overall virulence of the strain used could impact the outcome and interpretation of results.
authors: Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Bacterial Diseases Branch, 3156 Rampart Road, Fort Collins, CO 80521 USA. CMolins@cdc.gov.
authors: Claudia R
authors: CR
authors: Molins
authors: Mark J
authors: MJ
authors: Delorey
authors: Brook M
authors: BM
authors: Yockey
authors: John W
authors: JW
authors: Young
authors: John T
authors: JT
authors: Belisle
authors: Martin E
authors: ME
authors: Schriefer
authors: Jeannine M
authors: JM
authors: Petersen
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005604:Francisella tularensis / Q000145:classification* / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D008168:Lung / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D014406:Tularemia / Q000382:microbiology*; D014774:Virulence