Esx5 secretome in TB and TB-HIV pathogenesis and immunity

PROJECT SUMMARY Mycobacterium tuberculosis, the causative agent of human TB, lives exclusively in human cells, and to understand how it causes disease it is important to determine how it delivers its key pathogenic proteins into cells. Using specialized transduction, we generated the only reported complete genetic deletion of the esx5 locus encoding a transport system that is thought to secrete ~150 proteins out of the microbe, and we found that this esx5 mutant is a remarkably good live attenuated vaccine for preventing TB in animal models. In this study we will use our novel esx5 mutant to identify the specific proteins which it secretes, characterize the roles of these secreted proteins in causing disease, and determine the immunologic basis for why the mutant is such a good vaccine.