Evidence of nitrite acting as a stable and robust inducer of non-cultivability in Mycobacterium tuberculosis with physiological relevance

亚硝酸盐作为结核分枝杆菌不可培养性的稳定且有效的诱导剂的证据,具有生理相关性

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作者:Suwarna P Gample ,Sonia Agrawal ,Dhiman Sarkar

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.

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