Drug-Resistant Tuberculosis: From Molecular Targets to Treatment-Modifying Factors

Drug-resistant tuberculosis (DR-TB) remains a critical barrier to global disease control. While advances in dosing optimization have improved treatment regimens, significant gaps persist in understanding how drugs interact with their molecular targets, how resistance emerges at the population level, and how host and environmental factors modify treatment outcomes. Addressing these gaps requires integration across medicinal chemistry, preclinical pharmacology, and translational drug development.This Research Topic, hosted by the Pharmacology of Infectious Diseases section, seeks original research and reviews that connect molecular-level drug science with the real-world conditions under which DR-TB treatment succeeds or fails. We invite submissions of Original Research, Reviews, and Mini-Reviews addressing the following themes:1. Mechanisms of Action and the Emergence of ResistanceStudies elucidating the molecular targets of anti-TB agents and the biological basis of resistance, including genetic mutations, efflux pumps, ion transport systems, and metabolic adaptation in Mycobacterium tuberculosis. Of particular interest is work on induced resistance rates (for example, the global increase in bedaquiline-resistant strains) and whether induced resistance rates should be adopted as a criterion for advancing compounds through the development pipeline.2. Biofilms, Drug Penetration, and Preclinical Models (biofilms represent surviving bacteria; additional models can include: 1) planktonic — representing actively growing bacteria in optimal growth conditions; and 2) macrophage infection — representing intracellular bacterial growth during uptake, phagocytosis, and post-infection survival)This theme covers research into how biofilms drive drug tolerance in TB and ways to counter it. It includes developing preclinical lab tools (e.g., checkerboard assays, molecular models, synergy studies) and animal studies (mouse/rabbit) testing drug combinations against resistant TB forms and TB meningitis.3. Drug Discovery: Synthetic and Natural Product ApproachesIdentification and evaluation of novel antimycobacterial agents through rational synthesis (e.g., heterocyclic scaffolds, chalcone derivatives) or isolation from natural sources, including African medicinal plants. We also invite reviews profiling newer TB drugs in clinical development, covering pharmacological properties, synergy/antagonism in combination regimens, and known toxicities.4. Host and Environmental Modifiers of Drug EfficacyResearch on how host factors and environmental exposures alter drug pharmacology and bacterial response to treatment, including the impact of cigarette smoke, air pollution, and alcohol on antibiotic efficacy, and pharmacological interactions between anti-TB agents and drugs for common comorbidities (HIV, diabetes). This theme reflects the growing recognition that drug performance cannot be understood in isolation from the patient's biology and environment.5. Toxicity and Safety PharmacologyMechanistic investigations into adverse events associated with anti-TB therapy, with emphasis on cardiotoxicity linked to short-course regimen agents (BPaL drugs, clofazimine, moxifloxacin) and drug-induced liver injury (DILI). Studies must demonstrate direct relevance to pharmacological treatment.Authors must ensure their work aligns with the Pharmacology of Infectious Diseases mandate. This Research Topic excludes meta-analyses and retrospective clinical studies that lack substantial pharmacological analysis. Submissions must focus on the pharmacological aspects of drug-resistant TB treatment; work unrelated to these interventions will not be considered.Topic Editor Dr. Carol Nacy is the founder and CEO of Sequella, Inc. The other Topic Editors declare no competing interests with regard to the Research Topic subject. Topic editors: Carol Nacy, Moloko Caroline Cholo, Ofentse Mazimba Source: https://www.frontiersin.org/research-topics/80354/drug-resistant-tuberculosis-from-molecular-targets-to-treatment-modifying-factors