The first-line regimen, HRZE, for the treatment of tuberculosis (TB) was developed over 40 years ago and is long (6 months) and burdensome to patients and programs. Further, it has relatively low effectiveness (60-80% treatment success), low completion rates by 6 months of therapy, and is unforgiving to more than minor adherence lapses, leading to higher risk for relapse. For some patients, use of HRZE can be associated with toxicities such as liver and skin toxicity, as well as gastrointestinal side effects. For patients with drug-susceptible TB who have intolerance to first-line drugs, there are few options and no evidence-based alternative therapies. Until recently, multidrug-resistant TB (MDR-TB), required treatment for either 9-12 months (“short course”) with 7 drugs, many of which result in severe or irreversible toxicities, or 18-24 months (“standard duration”) with drugs that have significant treatment-limiting toxicities or that may have limited activity against MDR-TB strains due to low potency or unrecognized resistance. In this context, there was a second wave of TB drug development, which culminated in registration of bedaquiline (BDQ) in 2012 and pretomanid (Pa) in 2019, both for the treatment of drug-resistant TB, by the U.S. Food and Drug Administration (FDA). BDQ, Pa, and LZD (linezolid) (or BPaL) achieved 90% treatment success in patients with extensively drug resistant (XDR) or hard-to-treat MDR-TB, bringing hope that short-course regimens could be developed for all patients with pulmonary TB. In recent years, there has been a resurgence in TB drug development, which has produced a “third wave,” with multiple new chemical entities (NCEs) now in late preclinical or early clinical development. This study is an adaptive Phase 2 randomized, controlled, open-label, dose-ranging, platform protocol to evaluate the safety and efficacy of multidrug regimens for the treatment of adults with drug-susceptible pulmonary tuberculosis (TB). The adaptive design allows for regimens to be added during the trial for efficient testing of new drugs and drug combinations, identified as promising via translational modeling, against the standard of care (SOC) within the same trial infrastructure. Participants will be randomized to SOC (Arm 1) or to an experimental treatment arm. The treatment arms are; Arm 1 (SOC): isoniazid/rifampicin/pyrazinamide/ethambutol (HRZE) for 8 weeks and then isoniazid (INH)/rifampicin (RIF) for 18 weeks, for a total of 26 weeks of anti-TB treatment, at standard doses; Arm 2: bedaquiline (BDQ) 400 mg for 2 weeks and then 200 mg for 6 weeks + pretomanid (Pa) 200 mg for 8 weeks + linezolid (LZD) 600 mg for 8 weeks, followed by INH/RIF for 18 weeks, for a total of 26 weeks of anti-TB treatment; Arm 3A: BDQ 400 mg for 2 weeks and then 200 mg for 6 weeks + Pa 200 mg for 8 weeks + TBI-223 1200 mg for 8 weeks, followed by INH/RIF for 18 weeks, for a total of 26 weeks of anti-TB treatment; Arm 3B: BDQ 400 mg for 2 weeks and then 200 mg for 6 weeks + Pa 200 mg for 8 weeks + TBI-223 2400 mg for 8 weeks, followed by INH/RIF for 18 weeks, for a total of 26 weeks of anti-TB treatment; Arm 4A: BDQ 400 mg for 2 weeks and then 200 mg for 6 weeks + Pa 200 mg for 8 weeks + sutezolid (SZD) 800 mg for 8 weeks, followed by INH/RIF for 18 weeks, for a total of 26 weeks of anti-TB treatment; Arm 4B: BDQ 400 mg for 2 weeks and then 200 mg for 6 weeks + Pa 200 mg for 8 weeks + SZD 1600 mg for 8 weeks, followed by INH/RIF for 18 weeks, for a total of 26 weeks of anti-TB treatment. All drugs are given once daily. A total of 45 participants in each experimental treatment arm and at least 90 participants in the SOC arm will be enrolled, with each participant followed up for 52 weeks. Kericho site plans to enroll up to 100 participants across the study arms.