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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 S 4  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 S 4  belongs to the most virulent subspecies of  F. tularensis , subspecies  tularensis .    Methods  In this study, we investigated the relative virulence of Schu S 4  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 S 4  at drop point.    Results  Survival curve comparisons demonstrate that the Schu S 4  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 S 4  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 S 4  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.

bmc infectious diseases

Virulence difference between the prototypic Schu S4 strain (A1a) and Francisella tularensisA1a, A1b, A2 and type B strains in a murine model of infection