JHU scientists have engineered a gene expression construct to promote expression of a bacterial thymidine kinase in mycobacterium. Animal models are infected with the mycobacterium and then exposed to a radiolabeled thymidine kinase substrate. The substrate accumulates in the bacterium in the animal model to allow imaging and study of the localization of the TB infection. ADVANTAGES:
• Imaging technology allows animal model experiments that permit assessment of infection over time in fewer animals instead of sacrificing many animals to gather data from multiple time points for cheaper and faster studies of M. tuberculosis infection.
• Radiolabeled mycobacterial infections permits real-time imaging and non-invasive studies of TB infection that can potentially be adapted for use in larger animals that are better disease models.
• Reduction of the number of animals necessary to gather useful data will reduce costs associated with using larger animal models to speed testing and deployment of therapeutic compounds.
Tuberculosis (TB) is one of the leading infectious causes of morbidity and mortality worldwide. Experts estimate 1.7 million TB deaths per year worldwide, with 2 billion people suffering with latent TB infections. Diagnosis and treatment of TB and latent infection are still challenging. Animal models of experimental TB infection are expensive, time consuming and are not ideal for tracking the course of infection in a single animal. JHU scientists have developed a real-time, non-invasive imaging method to radiolabel and track Mycobacterium Tuberculosis infection in animal models to answer unmet these medical and research needs.
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• This imaging technology can be commercialized as a tool to complement or replace standard parameters used to evaluate TB disease in animal models to optimize research and development.
• This technology can be used to quantify tuberculosis infections in therapeutic drug screening applications, or evaluate response to anti-tuberculosis therapy for preclinical evaluation.
• This real time imaging technology can be used as a starting point to develop imaging technologies for diagnosing and monitoring M. tuberculosis bacterial burden in humans.
Sanjay Jain, William R. Bishai, Gyanu Lamichhane, Martin Pomper
Tuberculosis, mycobacterium, infectious, thymidine kinase, real-time
Allergy and Respiratory; Bioassay; Diagnostics; Diagnostics and measurement; Drug screening; Imaging; Infectious Diseases; Research Tools; Tuberculosis