F. tularensis Mouse Bioaerosol Model

Francisella tularensis, a Gram-type negative facultative intracellular coccobacillus, is the causative agent for tularemia, a serious and sometimes fatal disease of humans and animals. F. tularensis is considered one of the most infectious pathogenic bacteria due to the extraordinarily low inoculum (<10 CFU) that is required for infection, both through inhalation or inoculation. As a result, F. tularensis is considered a potential bioterrorism agent if released as an aerosol.

The development of medical countermeasures (MCMs) against aerosolized F. tularensis including antimicrobials or vaccines are actively under development since no effective vaccine against the aerosolized infection exists. Effective animal models are an important tool to further this research.

IITRl's bioaerosol system has proven to be highly effective in generating and stabilizing aerosolized bacteria for the inhalation infection in vaccine or antimicrobial challenge studies, with particles sizes generated within the respirable range. The system’s ability to deliver a high concentration of viable challenge material to each target animal is demonstrated by the spray factor, where spray factor represents the viable aerosol concentration / inoculum concentration of F. tularensis SCHU S4: 4.5 x 10-6. In addition, spray factors are stable across different concentrations for F. tularensis (Figure 1).

Figure 1. Spray Factor over a Range of F. tularensis SCHU S4 Concentrations
Figure 1. Comparison of Spray Factors across Y. pestis CO92 Concentrations

A lethal F. tularensis mouse model was developed using IITRI’s bioaerosol system to expose mice to increasing concentrations of aerosolized F. tularensis. The mouse model showed a direct relationship between dose exposure and lethality. The LD50 was determined to be 11.6 CFU/mouse.

Figure 2. Survival of BALB/c Mice at Different Exposure Concentrations of F. tularensis
Figure 2. Survival of BALB/c Mice at Different Exposure Concentrations of *F. tularensis*

For an example of this mouse model used in a challenge study, see: Grossman TH, Anderson MS, Christ D, Gooldy M, Henning LN, Heine HS, Kindt MV, Lin W, Siefkas-Patterson K, Radcliff AK, Tam VH, Sutcliffe JA. The Fluorocycline TP-271 Is Efficacious in Models of Aerosolized Francisella tularensis SCHU S4 Infection in BALB/c Mice and Cynomolgus Macaques. Antimicrob Agents Chemother. 2017 Jul 25;61(8).

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