Leveraging next-generation new approach methodology (NAM)-based systems to accelerate drug discovery and therapeutic development for drug-resistant mycobacterial diseases

Mycobacterial lung diseases, including tuberculosis (TB) and nontuberculous mycobacterial (NTM) infections, represent a critical global health challenge compounded by rapid antimicrobial resistance (AMR). Treating these infections is exceptionally difficult due to intrinsic resistance mechanisms and the protective, complex microenvironment of the human lung. Traditional 2D cell cultures and animal models routinely fail to predict drug efficacy and penetration, creating a major translational bottleneck in drug discovery. This therapeutic gap requires innovative, human-relevant testing platforms—specifically New Approach Methodologies (NAMs) like organoids, air-liquid interface (ALI) systems, and organ-on-a-chip (O-O-C) platforms. These advanced microphysiological systems recapitulate host-pathogen biology, allowing researchers to evaluate drug distribution, monitor bacterial persistence, and identify predictive biomarkers of antibiotic efficacy.Overall, this Research Topic aims to provide a comprehensive, interdisciplinary platform integrating microfluidics, biomaterials, pharmacology, and microbiology. The goal is to highlight how next-generation in vitro systems can be leveraged to accelerate antibiotic development, optimize treatment regimens, and evaluate novel host-directed therapies against mycobacterial pathogens. We invite submissions including original research, reviews, methods, and perspective articles addressing the following sub-themes of interest:• Evaluation of novel antibiotics and combination therapies using lung organoids and O-O-C platforms• NAM-based modelling of intrinsic and acquired resistance mechanisms in M. tuberculosis and NTM species (e.g., M. abscessus, MAC)• Predictive biomarkers of antibiotic efficacy and treatment response integrated with advanced multi-omics• Pharmacokinetics, drug penetration, and pharmacodynamics within bioengineered lung tissue models• In vitro evaluation of host-directed therapies and immunomodulatory agents alongside standard antibiotic regimens• Development, validation, and regulatory scaling of NAM-based infection models for high-throughput drug screening Topic editors: PAULO R. Z. ANTAS, Shafagh Al Nadaf Waters, Matt Johansen Source: https://www.frontiersin.org/research-topics/84402/leveraging-next-generation-new-approach-methodology-nam-based-systems-to-accelerate-drug-discovery-and-therapeutic-development-for-drug-resistant-mycobacterial-diseases