Mycobacterium Tuberculosis Dormancy and Resuscitation Mechanisms

Mycobacterium tuberculosis (Mtb) can enter a dormant state in response to host‐derived stresses such as hypoxia, nutrient limitation and nitrosative assault. In this non‐replicating persistence phase, bacilli adopt profound metabolic remodelling, down-regulating energy pathways and altering cell‐wall architecture to withstand antimicrobial pressure and immune clearance. Dormant populations evade detection by standard culture methods yet retain viability, posing challenges for diagnosis and treatment of latent infection. Reactivation or resuscitation from dormancy is mediated by specialised enzymes and signalling molecules that restore peptidoglycan turnover and central metabolism, enabling bacillary replication and disease recrudescence. Understanding the molecular determinants of dormancy entry and exit has global significance for improving diagnostics, shortening chemotherapy and preventing reactivation in millions of latently infected individuals worldwide.

Research from Nature Portfolio

Recent studies have shown that sustained release of nitric oxide within activated macrophages induces a population of differentially culturable Mtb that are undetectable on solid media yet viable in liquid culture when complemented by resuscitation-promoting factors (Rpfs). Exposure to a novel nitric oxide donor down-regulates endogenous rpf gene expression, generating a reversible non-culturable phenotype. Over-expression of Rpfs restores peptidoglycan remodelling and culturability, revealing a central role for host-derived reactive nitrogen species in dormancy induction and suggesting new avenues for enhancing diagnostic sensitivity and targeting latent bacilli.

Mycobacterium Tuberculosis Dormancy and Resuscitation Mechanisms publication trend

The graph below shows the total number of articles in mycobacterium tuberculosis dormancy and resuscitation mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Dormancy: A reversible non-replicating state in which Mtb down-regulates growth and metabolism to survive stress.

Resuscitation-promoting factors (Rpfs): Secreted peptidoglycan-hydrolysing enzymes that catalyse revival of dormant mycobacteria.

Differentially culturable tubercle bacteria (DCTB): Subpopulations of Mtb requiring specialised media or Rpfs for detection in culture.

Phenotypic tolerance: Transient drug insensitivity arising from metabolic down-regulation rather than genetic resistance.

Reactive nitrogen species (RNS): Host-derived molecules, notably nitric oxide, that modulate mycobacterial physiology and induce dormancy.

References

1. Nitric oxide induces the distinct invisibility phenotype of Mycobacterium tuberculosis. Communications Biology (2024).
2. Drug-Tolerant Mycobacterium tuberculosis Adopt Different Survival Strategies in Alveolar Macrophages of Patients with Pulmonary Tuberculosis. International Journal of Molecular Sciences (2023).
3. Computer-aided identification of Mycobacterium tuberculosis resuscitation-promoting factor B (RpfB) inhibitors from Gymnema sylvestre natural products. Frontiers in Pharmacology (2023).
4. Differentially culturable tubercle bacteria as a measure of tuberculosis treatment response. Frontiers in Cellular and Infection Microbiology (2023).