JOURNAL OF BACTERIOLOGY AND VIROLOGY ISSN:1598-2467(Print) 2093-0429(Online)

Tuberculosis (TB) remains a global public health crisis, responsible for approximately 1.3 million deaths annually. The effectiveness of current chemotherapy is limited by its inability to eradicate persister populations of Mycobacterium tuberculosis (Mtb), a minor fraction of phenotypic variants that exhibit high tolerance to TB antibiotics. Although the mechanisms underlying persister formation are not fully understood, accumulating evidence indicates that intermittent antibiotic exposure and innate immune pressures amplify persister formation, underscoring the importance of persister-specific adaptive metabolism. Mtb persisters arise through remodeling of central carbon and nitrogen metabolism, enabling survival under bactericidal oxidative stresses and facilitating entry into a latent TB infection state. This review summarizes recent advances in understanding the metabolic strategies employed by Mtb persisters to enhance intrinsic antibiotic tolerance and establish latent TB infection. The findings highlight metabolomics as a powerful tool for identifying previously unexplored metabolic signatures of Mtb persisters and for screening potential diagnostic biomarkers of persisters and drug-resistant TB.