Persistent and dormant tubercle bacilli and latent tuberculosis

Abstract

Tubercle bacillus has remarkable ability to persist in the human host and has caused latent infection in one third of the world population. The current tuberculosis (TB) chemotherapy while effective in killing growing bacilli is largely ineffective in killing persistent or dormant bacilli, leading to prolonged therapy. There is considerable recent interest to study mechanisms of persistence and dormancy in mycobacteria. Meanwhile, there is also confusion about the use of terminology of dormant and persistent bacilli. Different models of mycobacterial persistence have been established. Various mycobacterial factors have recently been identified that may be involved in persistence or dormancy and resuscitation of dormant organisms. The phenotypic resistance to antituberculosis drugs in persistent and dormant bacilli presents a major challenge for effective control of the disease. The host immune system is critical in controlling latent TB infection from reactivation. A recent interesting observation is the reactivation of latent TB infection by anti-TNF-alpha antibody used as a treatment for rheumatoid arthritis and Crohn's disease. The role of psychoneuroendocrinological factors in TB, which is often ignored in the era of modern chemotherapy but could be important for controlling latent infection, is also briefly reviewed. There is recent interest to develop new TB drugs that target persistent and dormant bacilli and also immunotherapeutic agents that enhance chemotherapy and better control latent infection. The complex interaction between the bacteria, drugs, host and the environment underscores the need for a combined approach that incorporates chemotherapy, immunotherapeutic agents, improved socioeconomic, nutritional and even conducive psychological factors for more effective control of TB and latent TB.

New insights into the function of granulomas in human tuberculosis

“…Based on the deciphering of the whole genome of M. tuberculosis in 1998 by Cole et al [26], gene expression profiling will provide new insights into mycobacterial processes during latent infection (see below [12]), ie during persistence in non-progressive tuberculous lesions (tuberculomas). The question remains as to whether the delicate balance between host immune response and pathogen is responsible for maintenance of latency, or whether M. tuberculosis shuts down all metabolic and replicative activities and remains inactive as long as a strong cellular immune response prevails in its microenvironment.…”

“…Successful containment of the pathogen to the site of the primary lesion results in latent infection, often morphologically seen as calcified granulomatous lesions. In more than 90% of all cases, this wellcontrolled state can be maintained, thus preventing active tuberculosis [11,12].…”

The C‐terminal of CysM from Mycobacterium tuberculosis protects the aminoacrylate intermediate and is involved in sulfur donor selectivity

“…These compounds are used by phagocytic cells to eliminate internalized bacteria [3,4], but several pathogens, for instance Salmonella typhimurium and M. tuberculosis, are able to escape elimination which leads to long term survival and persistent infection [5].…”

Mycobacterium aurum is Unable to Survive Mycobacterium tuberculosis Latency Associated Stress Conditions: Implications as Non-suitable Model Organism

“…Latent infection is characterized by an asymptomatic state of the population, acting as carrier of the infection. The current regimen of antimycobacterials is effective against active TB, but is largely ineffective in eliminating the M. tuberculosis latent infection [1,2], emphasizing the need for further studies in this direction.…”