A model for simultaneous evaluation of bacterial growth, gene expression and glucose metabolism in mice with bacterial infection

Objectives It is well known that infections can produce systemic responses. New imaging technology has been developed to monitor both gene expression and metabolic changes in vivo. In the case of the NF-ΚB luciferase reporter mouse, when NF-Κ:IKK B complex is phosphorylated in the cytoplasm, the NF-ΚB translocates to the cytoplasm where it binds to a specific promoter and activates the gene for luciferase. The analog of glucose, FDG, is phosphorylated and trapped in all tissues that use glucose and is used as a marker for glucose utilization in various tissues. In the present study we examined the association of Proteus mirabilis infection in the leg of mice on the subsequent stimulation of NF-ΚB expression and FDG uptake in vivo.

Methods Transgenic NF-ΚB luciferase mice were injected in the thigh with (5x10⁶ CFU) bioluminescent Proteus mirabilis. 24 hrs later the mice were anesthetized and imaged using a CCD camera. The mice were then injected with luciferin (1.0 mg IP) and reimaged. Finally, the mice were injected via tail vein with FDG (500 μCi/mouse) and imaged one hour later using a Concord P4 microPET camera.

Results At 24 hrs after injection, the Proteus mirabilis infected leg showed a dramatic level of bioluminescence. This was consistent with the rapid growth of the bacterium. At 30 minutes after injection of luciferin, there was significant bioluminescence on both dorsal and ventral images. This was consistent with the activation of the NF-ΚB luciferase in a number of tissues. Finally, microPET imaging demonstrated increased FDG uptake in the infected leg vs the contra-lateral uninfected leg.

Conclusions These studies demonstrate the feasibility of monitoring with whole body imaging the molecular events associated with growth of a bacterium, and the subsequent systemic changes induced by this infection at both the genetic and metabolic level.

Research Support Shriners Hospitals for Childre