Essential Reading

These publications offer additional context on the scientific ideas, translational strategies, and collaborative model that underpin the Tuberculosis Drug Accelerator (TBDA). For external audiences, they provide a useful path from consortium design and target discovery to lesion pharmacology, regimen optimization, and treatment shortening.

Consortium Design and Ecosystem

These pieces explain how TBDA itself is structured and governed, and how it fits into the broader TB discovery ecosystem. They are especially useful for funders, collaborators, and policy or communications audiences.

• Building and managing a complex drug discovery consortium
  Drug Discovery Today (July 2026), Volume 31, Issue 4, Article 104688.

  Focuses on how to design and run a complex multi-partner drug discovery consortium, using TBDA as a central example. Discusses governance, data-sharing, intellectual property, and culture in a way that is directly relevant to funders and institutional partners. On an external site, it complements the Nature Medicine TBDA commentary by showing how the consortium operates in practice.

• The Tuberculosis Drug Accelerator at year 10: what have we learned?
  Nature Medicine (2021).

  Provides the definitive consortium-authored overview of TBDA’s mission, design, and first-decade impact. Explains why TBDA was created, how the collaboration model works, and what scientific and organizational lessons emerged. For external visitors, it is the clearest anchor piece tying together many of the publications below.

• The tuberculosis drug discovery and development pipeline: 2014 overview
  Clinical Microbiology Reviews (2015).

  Lays out the tuberculosis pipeline and strategic challenges at a time when TBDA was ramping up. Gives readers a baseline sense of how sparse and fragile the pipeline once looked. That context makes TBDA’s later contributions and today’s richer regimen landscape easier to appreciate.

Regimen Design, Lesion Pharmacology, and Therapy Shortening

These readings show how TBDA and its partners think about whole regimens, lesion penetration, and treatment duration rather than single drugs in isolation.

• Discovery and development of a new oxazolidinone with reduced toxicity for the treatment of tuberculosis
  Nature Medicine (2026).

  Describes a next-generation oxazolidinone designed to retain efficacy while reducing key toxicities associated with linezolid. Shows how lessons from TBDA and related work are feeding into improved clinical candidates. Highlighting it signals active progress on real-world tolerability, not just adding compounds to the pipeline.

• Strategies for shortening tuberculosis therapy
  Nature Medicine (2025).

  Lays out mechanistic and translational strategies for achieving shorter, more effective tuberculosis regimens. Synthesizes insights from disease heterogeneity, lesion biology, and regimen design, and proposes ways to tailor duration to distinct patient groups. It shows that TBDA-aligned work is aimed at rational regimen-level problem solving, not only individual drugs.

• Tuberculosis drugs’ distribution and emergence of resistance in patients’ lung lesions: a mechanistic model and tool for regimen and dose optimization
  PLOS Medicine (2019).

  Builds a mechanistic model connecting intralesional drug concentrations, bacterial kill, and resistance emergence. Shows how lesion-level data can inform regimen choice and dosing before large clinical trials. This is a strong example of the quantitative, systems-pharmacology side of TBDA science.

• Efficient measurement and factorization of high-order drug interactions in Mycobacterium tuberculosis
  Science Advances (2017).

  Uses the DiaMOND framework to measure both pairwise and higher-order interactions among tuberculosis antibiotics and to identify new two-, three-, and four-drug synergies. Demonstrates how systematic interaction data can be turned into concrete regimen hypotheses rather than relying on ad hoc combinations. It helps make the regimen-optimization story more complete.

• Contribution of oxazolidinones to the efficacy of novel regimens containing bedaquiline and pretomanid in a mouse model of tuberculosis
  Antimicrobial Agents and Chemotherapy (2016).

  Shows how oxazolidinones contribute to the potency and sterilizing activity of bedaquiline-pretomanid-based regimens in mice. Provides a concrete example of how component drugs are tested and combined to build better regimens. It also bridges discovery-side work with the more clinical regimen story many visitors will already know.

• The association between sterilizing activity and drug distribution into tuberculosis lesions
  Nature Medicine (2015).

  Links drug penetration patterns in human tuberculosis lesions with sterilizing efficacy using mass-spectrometry imaging. Provides a foundational basis for the lesion-centric view of tuberculosis therapy that TBDA and its partners have embraced. It helps non-specialists understand why intralesional distribution matters as much as plasma pharmacokinetics or in vitro potency.

Target Discovery, Mechanisms, and Chemistry

These papers illustrate how TBDA-aligned teams discover and validate targets and then optimize chemotypes against them.

• Exploiting cAMP signaling in Mycobacterium tuberculosis for drug discovery
  Trends in Microbiology (2025).

  Discusses how cAMP signaling contributes to adaptation in host environments and how these pathways can be targeted therapeutically. Opens new target space beyond metabolism and respiration in a TBDA-relevant way. It broadens the reading list into signaling and host adaptation for visitors interested in emerging biology.

• Spirocycle MmpL3 inhibitors with improved hERG and cytotoxicity profiles as inhibitors of Mycobacterium tuberculosis growth
  ACS Omega (2021).

  Reports optimized MmpL3 inhibitors with improved safety properties, addressing common hERG and cytotoxicity issues seen in earlier series. Demonstrates TBDA-aligned refinement of whole-cell hits into more drug-like candidates. It shows that impact extends into safety and developability, not only potency.

• Opposing reactions in coenzyme A metabolism sensitize Mycobacterium tuberculosis to enzyme inhibition
  Science (2019).

  Shows how opposing reactions in coenzyme A metabolism create exploitable vulnerabilities in Mycobacterium tuberculosis. Connects deep pathway biology directly to druggability and illustrates TBDA-style mechanistic work. It gives readers a concrete, high-profile example of how new targets are identified.

• Targeting protein biotinylation enhances tuberculosis chemotherapy
  Science Translational Medicine (2018).

  Validates protein biotin ligase and biotinylation as bactericidal vulnerabilities that can synergize with existing tuberculosis drugs. Bridges genetic tools, chemical inhibition, and in vivo regimen shortening in a way that mirrors TBDA’s end-to-end approach. It offers a clear example of how target biology can translate into better combination therapy.

• Development of a novel lead that targets Mycobacterium tuberculosis polyketide synthase 13
  Cell (2017).

  Takes Pks13 from target concept through structurally characterized lead compounds with promising activity. Highlights the integration of structural biology, medicinal chemistry, and microbiology around a TBDA-priority target. It shows what successful target-based tuberculosis drug discovery can look like end to end.

• Validation of CoaBC as a bactericidal target in the coenzyme A pathway of Mycobacterium tuberculosis
  ACS Infectious Diseases (2016).

  Establishes CoaBC as essential and bactericidal, confirming coenzyme A biosynthesis as high-value terrain for tuberculosis drug discovery. Uses combined genetic and biochemical approaches in line with TBDA practice. It pairs well with the coenzyme A metabolism Science paper to tell a coherent story around this metabolic space.

• Fueling open-source drug discovery: 177 small-molecule leads against tuberculosis
  ChemMedChem (2013).

  Describes a large, openly shared set of phenotypic hits against Mycobacterium tuberculosis. Embodies the pre-competitive, data-sharing ethos that TBDA later scaled and formalized. It underscores that TBDA sits within a longer trajectory of collaborative, open tuberculosis drug discovery efforts.

Methods, Tools, and Collaborative Screens

These publications highlight methods and collaborative efforts that help TBDA prioritize combinations and candidates efficiently.

• An in vitro caseum-binding assay that predicts drug penetration in tuberculosis lesions
  TBDA-highlighted methods paper (2025).

  Measures how strongly compounds bind to caseum, a necrotic lesion matrix that can trap drugs and limit efficacy. Gives chemists and pharmacokinetic scientists an early readout on whether compounds are likely to penetrate lesion compartments that matter. It reinforces the message that TBDA pays close attention to lesion behavior, not only broth activity.

• Efficient Measurement of Drug Interactions with DiaMOND (Diagonal Measurement of N-way Drug Interactions)
  Methods in Molecular Biology (2021).

  Introduces a scalable way to quantify pairwise and higher-order drug interactions using a geometric sampling of dose space. Has been widely used in TBDA-aligned work to prioritize combinations before animal models or trials. It conveys that the consortium innovates in methodology as well as in targets and chemotypes.

• Identification of beta-lactams active against Mycobacterium tuberculosis by a consortium of pharmaceutical companies and academic institutions
  ACS Infectious Diseases (2022).

  Showcases a consortium approach to repurposing and optimizing a major antibiotic class for tuberculosis. Highlights how pharmaceutical partners and academics can jointly mine existing chemical space for overlooked anti-tuberculosis opportunities. On the site, it helps tell a story about TBDA’s role within a wider ecosystem of collaborative tuberculosis drug discovery.