Targeting Genome Integrity in Mycobacterium Tuberculosis: From Nucleotide Synthesis to DNA Replication and Repair

Miggiano, Riccardo; Morrone, Castrese; Rossi, Franca; Rizzi, Menico

doi:10.3390/molecules25051205

Cited by 18 publications

(13 citation statements)

References 103 publications

(147 reference statements)

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“…Various PPP intermediates that contribute to DNA and cell wall synthesis were detected to be altered in the ciprofloxacin-treated Mtb, [99,108,109]. Under normal circumstances, erythrose-4-phosphate and glyceraldehyde-3-phosphate produce xylulose-5-phosphate (xylulose-5P) and fructose-6-phosphate (fructose-6P) [91].…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

Elucidating the Antimycobacterial Mechanism of Action of Ciprofloxacin Using Metabolomics

et al. 2021

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“…Various PPP intermediates were detected to be altered in the ciprofloxacin treated Mtb, which contribute to DNA and cell wall repair [94,102,103]. Under normal circumstances, erythrose-4-phosphate and glyceraldehyde-3-phosphate produce xylulose-5-phosphate (xylulose-5P) and fructose-6-phosphate (fructose-6P) [91].…”

Section: Discussionmentioning

confidence: 99%

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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“…Nucleotides are the fundamental building units of RNA and DNA, the two polymers responsible for life’s biochemistry ( Azzam and Liu, 2013 ; Shivakumar et al, 2019 ; Miggiano et al, 2020 ; Cai et al, 2021 ). The investigation of their synthesis has made a substantial contribution to our understanding of chemical evolution and the chemical origins of life.…”

Section: Nucleoside Prebiotic Phosphorylation Mediated By P ...mentioning

confidence: 99%

Prebiotic Chemistry: The Role of Trimetaphosphate in Prebiotic Chemical Evolution

2022

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Life’s origins have always been a scientific puzzle. Understanding the production of biomolecules is crucial for understanding the evolution of life on Earth. Numerous studies on trimetaphosphate have been conducted in the field of prebiotic chemistry. However, its role in prebiotic chemistry has been documented infrequently in the review literature. The goal of this thesis is to review the role of trimetaphosphate in the early Earth’s biomolecule synthesis and phosphorylation. Additionally, various trimetaphosphate-mediated reaction pathways are discussed, as well as the role of trimetaphosphate in prebiotic chemistry. Finally, in our opinion, interactions between biomolecules should be considered in prebiotic synthesis scenarios since this may result in some advances in subsequent research on this subject. The research establishes an essential and opportune foundation for an in-depth examination of the “mystery of life".

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Targeting Genome Integrity in Mycobacterium Tuberculosis: From Nucleotide Synthesis to DNA Replication and Repair

Cited by 18 publications

References 103 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

Prebiotic Chemistry: The Role of Trimetaphosphate in Prebiotic Chemical Evolution

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