Time Course of Hematogenous Dissemination of Francisella tularensis A1, A2, and Type B in Laboratory Mice

Abstract

Tularemia is a tick-borne zoonotic bacterial disease. In the United States, human tularemia infections are caused by Francisella tularensis subspecies tularensis (Type A, clades A1 and A2) or F. tularensis subspecies holarctica (Type B). We developed a mouse model that can be used to study the ability of ticks to acquire and transmit fully virulent strains of F. tularensis (A1, A2, and Type B). We showed that 1) bacteremia was evident by 2 days post-infection (dpi) for A1, A2, and B, 2) bacteremia was expected to reach levels of > 10(8) cfu/mL by 3 dpi for A1 and A2 but not until 4 dpi for Type B, and 3) illness onset was delayed for mice exposed to Type B compared with A1 and A2. To maximize the likelihood of ticks acquiring infection from laboratory-infected mice before they become moribund and must be euthanized, ticks should be placed on mice so that periods of rapid engorgement occur 3-4 dpi for A1 and A2 and 4-5 dpi for Type B. Rigorous experimental studies of tick vector competence and efficiency conducted under standardized conditions are required to address several significant public health issues related to preventing and controlling tularemia. Our study provides the basis for a mouse model needed as the starting point to address these questions.