Tuberculosis (TB) is the most lethal infectious disease in human history, and prior to the COVID-19 pandemic was the leading cause of death from a single infectious agent globally, exceeding HIV. The COVID-19 pandemic has disrupted global TB control and is predicted to result in further increases in TB morbidity and mortality. Globally, the highest rates of drug-resistant TB have been reported from Eastern Europe, including the country of Georgia and other former Soviet republics. To meet the ambitious WHO End TB Strategy goals for 2035, new tools are urgently needed, including new and better drugs, improved diagnostics and an effective vaccine, as well as better implementation of existing tools. A shortage of well-trained TB investigators in Georgia and globally remains a key barrier to achieving the End TB Strategy goals. This renewal D43 application for the Emory-Georgia TB Research Training Program (EGTB-RTP) represents a collaboration between Emory University in Atlanta, GA, USA, and the 2 public health institutions in Tbilisi, Georgia, responsible for TB diagnostics, treatment, research and control: the National Center for Tuberculosis and Lung Disease (NCTLD) [lead Georgian institution] and the National Center for Disease Control and Public Health (NCDC) as well as collaboration with the Georgian AIDS Center and Ivane Javakhishvili Tbilisi State University (TSU). Much progress has been achieved since the initial funding of the EGTB-RTP in developing TB research infrastructure in Georgia, which was non-existent 16 years ago. Our program has provided long-term research training to 31 Georgians over 16 years helping to establish an emerging critical mass of MD and PhD-level investigators. Trainees in the EGTB-RTP have been highly productive with 92 TB-related publications during the current 5-year cycle of funding. NCTLD TB-related research funding has increased from <$5,000 per year when the EGTB-RTP was initiated to currently >$3 million per year. A major focus of an additional 5-year cycle of funding is the full transition of the leadership, management, and coordination of the research training program to Georgian investigators to ensure sustainability. To facilitate this transition, we propose an MPI format: Henry M. Blumberg, MD at Emory (PI of the EGTB-RTP since its inception) and Nestani Tukvadze, MD, a former Fogarty trainee who is now Director of the Clinical TB Research Unit at NCTLD and a leader of TB research in Georgia. Specific Aims of this renewal application include: 1) Transition program leadership, management, and training to Georgian investigators; 2) Continue to build human capacity to conduct high quality internationally recognized TB-related research in Georgia, focusing on long-term didactic and mentored research training to 12 new Fogarty trainees with outstanding potential; 3) Enhance research capacity and sustainability by providing leadership, mentor, and team science training; and 4) Focus on TB translational resea...