Studying modulation of AIM2 Inflammasome Activation in Response to F. tularensis LVS Mutants

F. tularensis is an intracellular Gram-negative bacterium that is the causative agent of the disease tularemia. The most lethal form of tularemia, the pneumonic form, can have up to a 50% mortality rate if left untreated, and there is currently no legalized vaccine for F. tularensis in the United States. When F. tularensisescapes from the phagosome into the cytosol of macrophages the innate immune system is alerted through the activation of the AIM2 inflammasome. The AIM2 inflammasome is a multiprotein complex that when activated leads to the cleavage of the cysteine protease caspase-1, which results in the processing and secretion of IL-1β and IL-18. The AIM2 inflammasome is crucial in mounting an innate immune response to F. tularensis. We therefore hypothesize that F. tularensis possess virulence mechanisms, which allows it to evade recognition by the AIM2 inflammasome. My studies are aimed at determining these virulence mechanisms by studying F. tularensis mutant strains that show altered activation of the AIM2 inflammasome. By determining the virulence mechanisms of F. tularensis we hope to develop an effective vaccine.

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