Mycobacterium tuberculosis Dormancy: How to Fight a Hidden Danger

Both latent and active TB infections are caused by a heterogeneous population of mycobacteria, which includes actively replicating and dormant bacilli in different proportions. Dormancy substantially affects M. tuberculosis drug tolerance and TB clinical management due to a significant decrease in the metabolic activity of bacilli, which leads to the complexity of both the diagnosis and the eradication of bacilli. Most diagnostic approaches to latent infection deal with a subpopulation of active M. tuberculosis, underestimating the contribution of dormant bacilli and leading to limited success in the fight against latent TB. Moreover, active TB appears not only as a primary form of infection but can also develop from latent TB, when resuscitation from dormancy is followed by bacterial multiplication, leading to disease progression. To win against latent infection, the identification of the Achilles' heel of dormant M. tuberculosis is urgently needed. Regulatory mechanisms and metabolic adaptation to growth arrest should be studied using in vitro and in vivo models that adequately imitate latent TB infection in macroorganisms. Understanding the mechanisms underlying M. tuberculosis dormancy and resuscitation may provide clues to help control latent infection, reduce disease severity in patients, and prevent pathogen transmission in the population.