Reduction and refinement of murine models of bacterial infection

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According to estimates by the World Health Organisation, in 2002 infectious diseases caused by bacteria, viruses and parasites killed 14.7 million people worldwide ? 26% of all deaths. In the search for better vaccines and drugs, scientists often use mice to investigate how these organisms cause disease. In such studies the first signs of disease are clinical symptoms like weight loss and ruffled fur. In this research we will develop genetic tools to make a number of infectious bacteria bioluminescent and use state of the art bioluminescence imaging (BLI) technology to refine existing mouse experiments. Using very sensitive cameras we can detect the light produced by bioluminescent bacteria from within an anaesthetised animal. Multiple imaging of the same animal over the course of an experiment allows the disease progression to be followed more accurately, while using less animals. As bioluminescence is quantifiable and related to bacterial numbers, the changing bioluminescent signal can be used to estimate whether an animal will survive or die and so allows for humane euthanasia perhaps even before the appearance of clinical symptoms. We will use this technology refine our protocols and reduce the numbers of animals in experiments.