Development and application of medaka and Mycobacterium marinum as an infection model for human tuberculosis

Human tuberculosis, caused by Mycobacterium tuberculosis, is the most common cause of death from a single infectious agent worldwide. Here I propose the use of the small fish medaka (Oryzias latipes) experimentally infected with Mycobacterium marinum as a model for human tuberculosis. To assist in tracking the progression of infection, I have used a strain of M. marinum expressing green fluorescent protein (Gfp). Fluorescence has enabled monitoring of the colonization of target organs. Furthermore, I have infected see-thourgh medaka with M. marinum expressing Gfp in order to monitor colonizaiton in vivo. The previously published zebrafish-M. marinum model was reevaluated under our experimental conditions and compared to medaka infections. The transcriptome of medaka infected with M. marinum has been surveyed using a medaka microarray in order to determine genes of interest for future studies. I have also conducted preliminary studies into the potential of chronic mycobacterial infection as a cancer promoter. By using a genetically tractable host such as medaka, invesitgation into both host and pathogen factors involved in mycobacterial pathogenesis are possible.