Abstract
Tuberculosis (TB) is the ninth leading cause of death worldwide, ranking above human immunodeficiency virus. Latency is the major obstacle in the eradication of this disease. How the physiology of the pathogen changes in transition to the latent stage needs to be understood. The latent bacteria extracted from animal hosts exist in a nonculturable (NC) phase, whereas bacteria extracted from most in vitro models are culture-positive. In the present study, we observed that nitrite, up to a concentration of 5 mM, shows the growth of Mycobacterium tuberculosis (MTB) in liquid media, but this effect starts reversing at higher concentrations. At a concentration of 10 mM, nitrite induces rapid nonculturability of MTB at the aerobic stage. This noncultivable dormancy was confirmed by analyzing the characteristics of NC bacteria. Further differential gene expression analyses clearly supported the formation of a dormancy phenotype. This study will be helpful for the use of this bacillus as a dormancy model in future studies on TB latency.
Highlights
Tuberculosis (TB) is one of the most ancient infectious diseases of mankind and is one of the top 10 causes of death worldwide, affecting a third of the global population[1]
Sodium nitrite has been reported to inhibit the growth of a wide variety of bacteria, such as Clostridia and Staphylococcus aureus[15]
In order to assess the effect of nitrite on Mycobacterium tuberculosis (MTB), we measured the OD620 and colony forming unit (CFU) count of MTB bacilli at different time points
Summary
Tuberculosis (TB) is one of the most ancient infectious diseases of mankind and is one of the top 10 causes of death worldwide, affecting a third of the global population[1]. It was observed that persistent and viable but noncultivable (VBNC) stages of MTB coexist and remain as part of the dormancy continuum. They could survive together as mixed population but differs in their physiological positions in the dormancy range[4]. In this study, we demonstrated that exposure of the MTB bacilli to nitrite induces dormancy under in vitro aerobic conditions. This dormancy is characteristically similar to the noncultivable type of dormancy, which was earlier reported and observed in isolates from in vivo animal models and humans. Our study provides a new insight into the development of noncultivable dormancy in MTB
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