Decoding drug resistance in <i>Mycobacterium tuberculosis</i> complex: genetic insights and future challenges

INTRODUCTION: (MTB) complicates TB eradication efforts. This review delves into the complexities of anti-TB drug resistance, its mechanisms, and implications on healthcare strategies globally. AREAS COVERED: We explore the genetic underpinnings of resistance to both first-line and second-line anti-TB drugs, highlighting the role of mutations in key genes. The discussion extends to advanced diagnostic techniques, such as Whole-Genome Sequencing (WGS), CRISPR-based diagnostics and their impact on identifying and managing drug-resistant TB. Additionally, we discuss artificial intelligence applications, current treatment strategies, challenges in managing MDR-TB and XDR-TB, and the global disparities in TB treatment and control, translating to different therapeutic outcomes and have the potential to revolutionize our understanding and management of drug-resistant tuberculosis. EXPERT OPINION: The current landscape of anti-TB drug resistance demands an integrated approach combining advanced diagnostics, novel therapeutic strategies, and global collaborative efforts. Future research should focus on understanding polygenic resistance and developing personalized medicine approaches. Policymakers must prioritize equitable access to diagnosis and treatment, enhancing TB control strategies, and support ongoing research and augmented government funding to address this critical public health issue effectively.