Mycobacterium tuberculosis in Focus: Advanced Strategies for Understanding and Overcoming Drug Resistance

Drug-resistant tuberculosis remains one of the most persistent infectious disease threats, driven in large part by Mycobacterium tuberculosis (Mtb)’s ability to adapt under drug pressure and survive in hostile host environments. Resistance to frontline agents such as isoniazid can emerge through multiple routes, including target modification, metabolic adaptation, and reduced intracellular drug accumulation via efflux systems. This article collection focuses on the antibiotic drug resistance mechanisms of Mycobacterium tuberculosis (Mtb) and explores innovative strategies to identify and study these mechanisms. It will highlight research on how Mtb develops resistance during drug therapy. Taking advantage of resistance discovery platforms, the collection will also explore the genetic basis of Mtb survival and virulence using methods such as transposon insertion sequencing to identify novel virulence factors and determine genetic requirements for in vivo survival. By curating a clearer, more integrated understanding of Mtb’s survival strategies, the collection aims to accelerate discovery of actionable vulnerabilities and inform future therapeutic targets.This collection welcomes submissions that expand our understanding of the following areas, among others.• How Mtb resistance emerges during therapy: stepwise evolution, within-host diversity, and selective pressures• Host mediated therapeutic options for shortening of tuberculosis therapy• Phenotypic drug resistance in Mtb: tolerance and persistence• Efflux-mediated resistance: regulation, substrate range, and contribution to isoniazid and multidrug resistance• Cell envelope permeability and transport as barriers to antibiotic entry and drivers of reduced drug accumulation• Mechanisms of drug resistance, including prodrug activation pathways, oxidative stress responses, and compensatory adaptations• Chemical-genetic interaction characterizations that link drug activity to bacterial pathways and reveal synergistic combinations• Transposon insertion sequencing (TnSeq) to identify genes required for survival under drug stress and in infection models• Genetic requirements for in vivo survival, persistence, and relapse, including niche-specific essential genes• Discovery and characterization of novel virulence factors that intersect with resistance, tolerance, and immune evasion• Metabolic adaptations and redox homeostasis that support survival under antibiotic and host-imposed stresses• Intrabacterial xenobiotic metabolism limitation of drug accumulation• Regulatory networks (transcriptional regulators, two-component systems, small RNAs) controlling resistance and stress adaptation• Strategies to translate mechanism into therapy: efflux pump inhibition, regimen design to suppress resistance trajectories, and target prioritization for new drugs Topic editors: NITIN PAL KALIA, Sanpreet Singh, Ruslana Bryk, Stephanie Petrella Source: https://www.frontiersin.org/research-topics/77342/mycobacterium-tuberculosis-in-focus-advanced-strategies-for-understanding-and-overcoming-drug-resistance