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ABSTRACTBioluminescence imaging (BLI) enables real-time, noninvasive tracking of infection in vivoand longitudinal infection studies. In this study, a bioluminescent Francisella tularensisstrain, SCHU S4-lux, was used to develop an inhalational infection model in BALB/c mice. Mice were infected intranasally, and the progression of infection was monitored in real time using BLI. A bioluminescent signal was detectable from 3 days postinfection (3 dpi), initially in the spleen and then in the liver and lymph nodes, before finally becoming systemic. The level of bioluminescent signal correlated with bacterial numbers in vivo, enabling noninvasive quantification of bacterial burdens in tissues. Treatment with levofloxacin (commencing at 4 dpi) significantly reduced the BLI signal. Furthermore, BLI was able to distinguish noninvasively between different levofloxacin treatment regimens and to identify sites of relapse following treatment cessation. These data demonstrate that BLI and SCHU S4-luxare suitable for the study of F. tularensispathogenesis and the evaluation of therapeutics for tularemia.

Whole body imaging technologies, coupled with the generation of stable light emitting strains of infectious agents, make it possible to monitor the location and kinetics of agent growth inside an animal by noninvasive nonterminal methodologies throughout the course of the infection. However, imaging of viable hazardous pathogens, such as Yersinia pestis, requires specialized containment facilities to prevent contamination of both personnel and the wider environment. Here we describe the successful establishment of an in vivobioimaging capability specifically addressing the requirement for safe and secure work with hazard group 3 pathogens and demonstrate its utility for imaging mice infected with a bioluminescence producing strain of Y. pestis.