Intermediary metabolism of mycobacteria

Ramakrishnan, T. V.; Murthy, P. S.; Gopinathan, K. P.

doi:10.1128/br.36.1.65-108.1972

Cited by 31 publications

(6 citation statements)

References 289 publications

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“…These workers found 97% of total cytochromes b, c, and a + a3 in a membrane "ghost" preparation from M. phlei. Although oxidative phosphorylation in ghosts was only slightly lower than that found in electron transport particles (ETP; see review of intermediary metabolism by Rhamakrishnan et al [958] and that of Goldman [435] regarding enzyme systems of mycobacteria), ghosts did not couple phosphorylation to oxidation. Most adenosine triphosphatase (ATPase) activity was associated with ghosts, as was malate-vitamin K reductase.…”

Section: Cytoplasmic Membrane System Mesosomes Cytochromes Iron-chelating Compoundsmentioning

confidence: 78%

Mycobacterium

Barksdale¹,

Kim²

1977

Bacteriol Rev

134

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M. xenopi ( 1037) M. paraffinicum (292) M. kansasii (198; 500) M. scrofulaceum (940; 941) 1950 M. terrae (978; 1225)c M. intracellulare (275; 996)d M. ukerans (746; 370) M. fortuitum (276, see also reference 519) M. microti (1246; 963)e M. thamnopheos (53)' M. marinum (52) M. chelonei (403; 126),g M. lepraemurium (1094; 769) M. phlei (842; 713)h M. bovis (1070; 585) M. paratuberculosis (552, 1188; 126)Y M. avium (1104, 754; 244, see also [717]) M. smegmatis (30; 713) M. tuberculosis (623; 712) M. keprae (species forma, 489, 712)J 220 BARKSDALE AND KIM BACTERIOL. REV.

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Section: Cytoplasmic Membrane System Mesosomes Cytochromes Iron-chelating Compoundsmentioning

confidence: 78%

Mycobacterium

Barksdale¹,

Kim²

1977

Bacteriol Rev

134

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“…FAS I and FAS II provide acyl-groups for the synthesis of all cell wall components except for AG [38,46,47]. C14:0, C16:0, C18:0, ∆ 9 C16:1, and ∆ 9 C18:1 are considered major fatty acids of the glycerolipids and mycolic acids [48][49][50]. C16:0 and C18:0 are oxidized, in the presence of Fe 2+ , a flavin, NADPH, and O 2 , to produce ∆ 9 C16:1 and ∆ 9 C18:1, respectively [51,52].…”

Section: Discussionmentioning

confidence: 99%

Elucidating the Antimycobacterial Mechanism of Action of Decoquinate Derivative RMB041 Using Metabolomics

et al. 2021

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Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), still remains one of the leading causes of death from a single infectious agent worldwide. The high prevalence of this disease is mostly ascribed to the rapid development of drug resistance to the current anti-TB drugs, exacerbated by lack of patient adherence due to drug toxicity. The aforementioned highlights the urgent need for new anti-TB compounds with different antimycobacterial mechanisms of action to those currently being used. An N-alkyl quinolone; decoquinate derivative RMB041, has recently shown promising antimicrobial activity against Mtb, while also exhibiting low cytotoxicity and excellent pharmacokinetic characteristics. Its exact mechanism of action, however, is still unknown. Considering this, we used GCxGC-TOFMS and well described metabolomic approaches to analyze and compare the metabolic alterations of Mtb treated with decoquinate derivative RMB041 by comparison to non-treated Mtb controls. The most significantly altered pathways in Mtb treated with this drug include fatty acid metabolism, amino acid metabolism, glycerol metabolism, and the urea cycle. These changes support previous findings suggesting this drug acts primarily on the cell wall and secondarily on the DNA metabolism of Mtb. Additionally, we identified metabolic changes suggesting inhibition of protein synthesis and a state of dormancy.

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“…Valine also serves as a precursor of propionyl-CoA [116,123] and is used for the elongation of odd-chain fatty acids [124]. Aspartic acid additionally is the precursor of NAD + , 2,6-diaminopimelate (DAP) [125,126], and S-adenosyl methionine (SAM) [127]. Considering this, NAD + is subsequently an important cofactor for FAS I [128], and SAM is required for the methylation of cell-wall fatty acids [129].…”

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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Intermediary metabolism of mycobacteria

Cited by 31 publications

References 289 publications

Mycobacterium

Mycobacterium

Elucidating the Antimycobacterial Mechanism of Action of Decoquinate Derivative RMB041 Using Metabolomics

Elucidating the Antimycobacterial Mechanism of Action of Ciprofloxacin Using Metabolomics

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