Models of Latent Tuberculosis: Their Salient Features, Limitations, and Development

Abstract

Latent tuberculosis is a subclinical condition caused by Mycobacterium tuberculosis, which affects about one-third of the population across the world. To abridge the chemotherapy of tuberculosis, it is necessary to have active drugs against latent form of M. tuberculosis. Therefore, it is imperative to devise in vitro and models of latent tuberculosis to explore potential drugs. In vitro models such as hypoxia, nutrient starvation, and multiple stresses are based on adverse conditions encountered by bacilli in granuloma. Bacilli experience oxygen depletion condition in hypoxia model, whereas the nutrient starvation model is based on deprivation of total nutrients from a culture medium. In the multiple stress model dormancy is induced by more than one type of stress. In silico mathematical models have also been developed to predict the interactions of bacilli with the host immune system and to propose structures for potential anti tuberculosis compounds. Besides these in vitro and in silico models, there are a number of in vivo animal models like mouse, guinea pig, rabbit, etc. Although they simulate human latent tuberculosis up to a certain extent but do not truly replicate human infection. All these models have their inherent merits and demerits. However, there is no perfect model for latent tuberculosis. Therefore, it is imperative to upgrade and refine existing models or develop a new model. However, battery of models will always be a better alternative to any single model as they will complement each other by overcoming their limitations.

Design, Synthesis, and Characterization of N-Oxide-Containing Heterocycles with in Vivo Sterilizing Antitubercular Activity

“…According to an estimate, one-third of the world’s population is infected with a latent form of TB, 2 for which treatment is often ineffective owing to a lack of drugs with the ability to act on mycobacteria in the dormant state. 3 , 4 …”

Resistance related metabolic pathways for drug target identification in Mycobacterium tuberculosis

“…These include samples, conditions and the statistically significant measurements ( p -value) for each experiment. Conditions most often associated with persistence have been reported as hypoxia, starvation and change in PH [ 37 ]. Additionally, the lack of close homologs to human gut flora would facilitate the design of M. tuberculosis specific drugs and inform in vivo mouse infection studies.…”

Modelling a Silent Epidemic: A Review of the <em>In Vitro </em>Models of Latent Tuberculosis

“…It is important to note that M. tuberculosis cannot survive if placed straight into NRP stage II conditions: the process of steady decrease in oxygen saturation in NRP stage I is necessary to achieve NRP stage II [36]. Hypoxia is confirmed by the decolourisation of methylene blue (concentration of 1.5 µg/mL) and by a stabilisation of the growth curve into a plateau [38], sometimes referred to as an early stationary phase. Under this model, M. tuberculosis is indifferent to the presence of Isoniazid (INH) but the presence of Metronidazole (MET) has a bactericidal affect [39].…”