Beyond culturability: VBNC-like and differentially culturable Mycobacterium tuberculosis challenge growth-based...

Culturability remains the predominant method for assessing bacterial viability in tuberculosis research and clinical practice. However, growth-based detection provides only a limited and context-dependent dimension of Mycobacterium tuberculosis (MTB) survival. MTB populations may evade recovery by standard culture while retaining molecular, metabolic, or functional features inconsistent with irreversible cellular death, resulting in persistent discrepancies between culture outcomes and other biological or clinical indicators. This review explores viable but non-culturable (VBNC)-like phenotypes and differentially culturable tubercle bacilli (DCTB) as detection-defined frameworks for interpreting such growth-invisible populations. We analyze their methodological foundations and interpretative limitations, emphasizing that neither reflects a discrete or stable physiological state. Integrating evidence from resuscitation assays, molecular viability measurements, and clinical observations, we propose a continuum-based interpretation of MTB viability in which bacterial populations occupy diverse physiological states spanning survival potential and growth competence. Within this framework, apparent non-culturability is more accurately conceptualized as a conditional result of physiological limitations and methodological sensitivity, rather than as conclusive evidence of bacterial death or dormancy. This perspective provides a coherent conceptual foundation for interpreting bacterial persistence, clearance, and treatment response in tuberculosis.