The overall objectives of the consortium are (i) to discover and develop novel TB drug candidates targeting various aspects of bacterial proteostasis (the capacity to coordinately synthesize and degrade proteins), and (ii) to combine these candidates into novel 3- or 4-drug regimens capable of shortening the treatment of drug-susceptible or RR-TB. The overarching goal is to develop one or more pharmacodynamically-optimized, universally active, treatment-shortening regimens targeting Mtb proteostasis. Because this effort will occur in the context of a robust, highly collaborative TB drug development program sponsored by TB Alliance pre-clinical candidates emerging from Projects 1-4 may also be combined with other promising pre-clinical leads/candidates and clinical candidates that target mechanisms other than proteostasis, thus amplifying the potential opportunities for discovery of transformational regimens.