Mycobacterium tuberculosis: Dormancy, Persistence and Survival in the Light of Protein Synthesis

Kumar, Ranjeet; Sanyal, Suparna

doi:10.5772/31098

Cited by 5 publications

(6 citation statements)

References 91 publications

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“…However, as will be explained, glucose and glycerol seem to be the major suppliers for such, and for the various components required for DNA repair. This is supported by previous findings indicating ROS, produced during the FQ-induced SOS-response, causes oxidative stress, which in turn activates utilization of triacylglycerol (TAG) and cell wall lipids for energy [97][98][99], as is generally the case during the non-replicative phase of Mtb [100,101]. These results are also supported by previous findings showing reduced concentrations of phospholipids and mycolic acids in the cell wall macromolecules of sub-MIC ciprofloxacintreated M. smegmatis [47], because these are now being preferentially used for energy production, with glucose supplying the necessary carbon substrates for the continued synthesis of these much-needed fatty acids, which are now preferentially used for energy production.…”

Section: Discussionsupporting

confidence: 85%

Elucidating the Antimycobacterial Mechanism of Action of Ciprofloxacin Using Metabolomics

et al. 2021

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In the interest of developing more effective and safer anti-tuberculosis drugs, we used a GCxGC-TOF-MS metabolomics research approach to investigate and compare the metabolic profiles of Mtb in the presence and absence of ciprofloxacin. The metabolites that best describe the differences between the compared groups were identified as markers characterizing the changes induced by ciprofloxacin. Malic acid was ranked as the most significantly altered metabolite marker induced by ciprofloxacin, indicative of an inhibition of the tricarboxylic acid (TCA) and glyoxylate cycle of Mtb. The altered fatty acid, myo-inositol, and triacylglycerol metabolism seen in this group supports previous observations of ciprofloxacin action on the Mtb cell wall. Furthermore, the altered pentose phosphate intermediates, glycerol metabolism markers, glucose accumulation, as well as the reduction in the glucogenic amino acids specifically, indicate a flux toward DNA (as well as cell wall) repair, also supporting previous findings of DNA damage caused by ciprofloxacin. This study further provides insights useful for designing network whole-system strategies for the identification of possible modes of action of various drugs and possibly adaptations by Mtb resulting in resistance.

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Section: Discussionsupporting

confidence: 85%

Elucidating the Antimycobacterial Mechanism of Action of Ciprofloxacin Using Metabolomics

et al. 2021

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“…However, as will be explained, glucose and glycerol seem to be the major suppliers for such, and the various components required for DNA repair. This is supported by previous findings indicating ROS, produced during the FQ-induced SOS-response, causes oxidative stress, which in turn activates utilization of triacylglycerol (TAG) and cell wall lipids for energy [92][93][94], as is generally the case during the non-replicative phase of Mtb [95,96]. These results are also supported by previous findings showing reduced concentrations of phospholipids and mycolic acids in the cell wall macromolecules of sub-MIC ciprofloxacin-treated M. smegmatis [47], since these are now being preferentially used for energy production, with glucose supplying the necessary carbon substrates for the continued synthesis of these much-needed fatty acids which are now preferentially used for energy production.…”

Section: Discussionsupporting

confidence: 85%

Elucidating the antimycobacterial mechanism of action of ciprofloxacin using metabolomics

Knoll¹,

Lindeque²,

Adetomiwa³

et al. 2021

Preprint

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In the interest of developing more effective and safer anti-Tuberculosis treatment, we aimed for a better understanding of the antimycobacterial action of ciprofloxacin against Mycobacterium tuberculosis (Mtb). We used GCxGC-TOF-MS and well described metabolomics statistical approaches, to investigate and compare the metabolic profiles of Mtb in the presence and absence of the drug. The metabolites that best describe the differences between the compared groups were identified as markers characterizing the changes induced by ciprofloxacin. Malic acid was ranked as the most significantly altered metabolite marker induced by ciprofloxacin, indicative of an inhibition of the tricarboxylic acid (TCA) and glyoxylate cycle of Mtb. The altered fatty acid, myo-inositol and triacylglycerol metabolism seen in this group, supports the previous observations of ciprofloxacin action on the Mtb cell wall. Furthermore, the altered pentose phosphate intermediates, glycerol metabolism markers, glucose accumulation, and the reduction in the glucogenic amino acids specifically, indicates a flux towards DNA (as well as cell wall) repair, also supporting previous findings of DNA damage caused by ciprofloxacin. This study further provides insights useful for designing network whole-system strategies for the identification of possible modes of actions of various drugs and possibly adaptations by Mtb resulting in resistance.

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“…In the persistent phase, metabolism is shifted from glucose to lipids, glycolysis is downregulated, and the glyoxylate shunt is upregulated, allowing anaplerotic maintenance of TCA cycle 39–41 .…”

Section: Resultsmentioning

confidence: 99%

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

Gample

Agrawal

Sarkar

2019

Sci Rep

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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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Mycobacterium tuberculosis: Dormancy, Persistence and Survival in the Light of Protein Synthesis

Cited by 5 publications

References 91 publications

Elucidating the Antimycobacterial Mechanism of Action of Ciprofloxacin Using Metabolomics

Elucidating the Antimycobacterial Mechanism of Action of Ciprofloxacin Using Metabolomics

Elucidating the antimycobacterial mechanism of action of ciprofloxacin using metabolomics

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

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