Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026918 (Mycobacterium)
 52,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The susceptibility to H2O2 of 5 strains of Mycobacterium intracellulare and both catalase-positive (TMC 102) and negative (TMC 303) strains of M. tuberculosis, H37RV, was tested at pH 7.0 and 4.0. All strains of M. intracellulare were significantly more resistant to this oxygen metabolite than were the two M. tuberculosis strains, even though the catalase activity of M. tuberculosis TMC 102 was higher than most M. intracellulare strains. Even the catalase negative (Eggeman) strain of M. intracellulare showed greater resistance to 0.2% H2O2 than M. tuberculosis H37RV (TMC 102). This suggests that M. intracellulare is protected from H2O2 damage by factors additional to their catalase activity.
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PMID:Susceptibility of Mycobacterium intracellulare to hydrogen peroxide. 643 58

Trehalose diesters (natural 6,6'-trehalose dimycolate from Mycobacterium tuberculosis or synthetic (a 76 carbon atom analogue)), when suspended in water, give stable and well-defined emulsions. These emulsions, injected i.p. in mice significantly limit the growth of P815 syngeneic mastocytoma cells. They elicit macrophages with a cytostatic activity against P815 cells in vitro, strong enough to be expressed at low effector to target ratios (E/T = 1.4) or after a short coincubation period (2 hr). The antitumor potential of these macrophages seems to coincide with their ability to release H2O2 upon pharmacologic triggering. Depressed levels of alkaline phosphodiesterase and beta-galactosidase are proposed as other biochemical markers of cytostatic macrophages.
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PMID:Antitumor activity and hydrogen peroxide release by macrophages elicited by trehalose diesters. 680 86

Among isoniazid-sensitive strains of Mycobacterium tuberculosis, strong associations were found in 56 strains of phage type A and I from India, Burma and East Africa between attenuation in the guinea-pig, a low content of strongly acidic (SAL) and sulphatide (SL) lipids, the presence of the attenuation indicator (AI) lipid and phage type I, suggesting that lipid content might mediate attenuation. However, 22 strains of phage type B and I from Iran and Britain also had low contents of SAL and SL but were highly virulent. Although the finding of a strong association in all 78 strains between attenuation and H2O2 susceptibility in vitro supports other evidence that attenuation is often due to increased susceptibility to H2O2 secreted by macrophages, an alternative mediator of virulence probably exists since 8 of the strains were attenuated and also resistant to H2O2. Identification of South Indian attenuated strains for epidemiological purposes by in vitro tests would be best achieved by the presence of AI, H2O2 susceptibility and, if the strains originated in or near India, by phage type I.
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PMID:Role of lipid content and hydrogen peroxide susceptibility in determining the guinea-pig virulence of Mycobacterium tuberculosis. 681 80

L-Lactate oxidase from Mycobacterium smegmatis catalyzes the oxidative decarboxylation of glycollate, with formate, CO2, and H2O as the major products. In addition, some "uncoupling" of the normal reaction occurs, with glyoxylate and H2O adition, some "uncoupling" of the normal reaction occurs, with glyoxylate and H2O2 as products. Glyoxylate is also a substrate (presumably as its hydrate); in this case, the reaction products are oxalate and H2O2. Evidence is presented that the enzyme recognizes glycollate as a prochiral substrate, differentiating between the Re- and Si-faces of the alpha carbon atom. Two highly fluorescent species are formed concomitantly from the reaction with glycollate; they are proposed to be covalent alpha-glycollyl adducts to the reduced flavin position N(5). One of these adducts is labile and in rapid equilibrium with oxidized enzyme and glycollate, and with the complex of reduced enzyme and glyoxylate; this adduct is a catalytically competent intermediate. The other adduct is comparatively stable (t 1/2 for decay = 20 min at 25 degrees C) and does not react with O2. It is formed at a rate approximately 1% that of the catalytic adduct, but because of its lack of reaction with O2 and its stability, it gradually accumulates during catalytic turnover, resulting in catalytically incompetent enzyme. An isotope effect of approximately 4 is found in the reduction of oxidized enzyme flavin and in the formation of the labile fluorescent adduct, when alpha-2H2-glycollate or (R)-glycollate-2-d is used, but not with the (S)-glycollate-2-d enantiomer. It is concluded that the catalytic adduct is formed by hydrogen abstraction from the Re-face of glycollate.
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PMID:Studies on the reaction mechanism of lactate oxidase. Formation of two covalent flavin-substrate adducts on reaction with glycollate. 735 9

The physical properties and activities of the purified catalase-peroxidase hydroperoxidase I (HPI) of Escherichia coli (EcHPI) and HPI with a carboxyl-terminal extension of Mycobacterium tuberculosis (MtHPI-e) are compared to those of commercial preparations of horseradish peroxidase (HRP). The catalase-peroxidase proteins had similar absorption spectra and differed primarily in that MtHPI-e has a higher peroxidatic to catalatic activity ratio than EcHPI. Trypsin cleavage of MtHPI-e resulted in the formation of an active catalase-peroxidase lacking the carboxyl-terminal extension. The three enzymes, HRP, MtHPI-e, and EcHPI, mediated the isoniazid- and H2O2-dependent production of radical species, as detected by nitroblue tetrazolium reduction. A constant flux of H2O2, generated in situ from glucose oxidase and glucose was used. MtHPI-e was more effective at isoniazid-dependent radical production than EcHPI and HRP. Similar qualitative results were obtained by staining nondenaturing polyacrylamide gels for activity with nitroblue tetrazolium in the presence of isoniazid and H2O2. The absorbance spectrum of HRP exhibited changes during incubation with isoniazid and H2O2 consistent with the formation of several typical reaction intermediates, whereas the catalase-peroxidases exhibited no distinct spectral changes. The results suggest that the sensitivity of M. tuberculosis to isoniazid may be the result of isoniazid-dependent radical formation by the catalase-peroxidase in the absence of other catalase activities to remove substrate H2O2.
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PMID:Comparison of isoniazid oxidation catalyzed by bacterial catalase-peroxidases and horseradish peroxidase. 748 9

We have previously demonstrated that growth hormone (GH) is a human macrophage-activating factor which primes monocytes for enhanced production of H2O2 in vitro. This report extends our observations to other monocyte functions relevant to infection. We find that GH also primes monocytes for O2- production, to a degree similar to the effect of gamma interferon. Neither macrophage-activating factor alone stimulates monocytes to release bioactive tumor necrosis factor. However, GH, unlike gamma interferon, does not synergize with endotoxin for enhanced tumor necrosis factor production. In further contrast, GH does not alter monocyte adherence or morphology, while phagocytosis and killing of Mycobacterium tuberculosis by GH-treated monocytes are also unaffected. Therefore, despite the multiplicity of the effects of GH on the immune system in vivo, its effects on human monocytes in vitro appear to be limited to priming for the release of reactive oxygen intermediates.
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PMID:Growth hormone activation of human monocytes for superoxide production but not tumor necrosis factor production, cell adherence, or action against Mycobacterium tuberculosis. 759 Oct 64

Using phosphorimager technology to quantitate differences in protein expression, we have investigated the modulation of protein synthesis by Mycobacterium tuberculosis in response to intracellular residence in human macrophages and, for comparison, in response to various stress conditions during extracellular growth. Proteins of M. tuberculosis growing intracellularly in human THP-1 cells and extracellularly in broth were labeled with [35S]methionine; during intracellular growth, host cell protein synthesis was inhibited with cycloheximide. The metabolically labeled proteins were separated by two-dimensional gel electrophoresis and quantitatively analyzed. Intracellular residence in macrophages induced a profound change in the overall phenotype of M. tuberculosis. The expression of at least 16 M. tuberculosis proteins was induced (at least a twofold increase compared with growth in broth) and 28 proteins repressed (at least a twofold decrease). Many of the phenotypic changes in protein expression induced during intracellular growth occurred during extracellular growth in response to stress conditions including heat-shock, low pH, and H2O2. However, the pattern of induced and repressed proteins was unique to each stress condition. Of the 16 macrophage-induced proteins, 6 were absent during extracellular growth under both normal and stress conditions. Such proteins are potential virulence determinants and/or they may be important in the cell-mediated and protective immune response to M. tuberculosis infection.
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PMID:Identification of macrophage and stress-induced proteins of Mycobacterium tuberculosis. 761 94

TGF-beta at 1 and 10 ng/ml inhibited H2O2 production and fibronectin adherence by human monocytes. Coculture with anti-TGF-beta Abs or with IFN-gamma, but not with growth hormone, abrogated these effects. Neither viability nor superoxide production were decreased by TGF-beta treatment. TGF-beta appeared to be inhibiting H2O2 production rather than inducing catalase as preincubation in azide was without effect. Also, TGF-beta did not inhibit activity against virulent Mycobacterium tuberculosis. Coculture of monocytes with IFN-gamma + TGF-beta in vitro moderately inhibited the growth of M. tuberculosis when compared with untreated cells. Phagocytosis was not inhibited. Treatment of monocytes with another combination of cytokines, IFN-gamma+ TNF-alpha + vitamin D3, markedly reduced bacterial viability, although this appeared to be due to decreased phagocytosis leading to extracellular death of the bacteria. We conclude that despite suppressing some monocyte functions such as H2O2 production and adherence, TGF-beta, in combination with other cytokines, leaves other antimicrobial functions of the monocyte unaffected or even enhanced.
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PMID:Selective deactivation of human monocyte functions by TGF-beta. 767 31

Escherichia coli strains were previously found to be susceptible to the antituberculosis drug isonicotinic acid hydrazide (isoniazid [INH]) when they carried certain mutations that also sensitize them to peroxides: a deletion in oxyR, a redox-sensitive regulator of hydrogen peroxide-inducible genes, or mutations in both katG and ahpCF, OxyR-regulated genes encoding hydroperoxidase I, and an alkyl hydroperoxide reductase. To test whether INH, like peroxides, activates OxyR, the effect of INH on OxyR regulation was examined. Primer extension assays showed that transcription of the OxyR-regulated oxyS gene was not significantly induced by INH in wild-type cells, indicating that INH does not activate OxyR. However, the INH-susceptible katG ahpCF mutant strain was found to have constitutively high levels of oxyS transcription. This suggested that the lack of peroxidase expression in these strains allows endogenous oxidants to accumulate, and this leads not only to constitutive OxyR activation but also to INH susceptibility. Consistent with this concept, hydrogen peroxide or cumene hydroperoxide potentiated the INH susceptibilities of wild-type cells, while the antioxidant ascorbic acid protected the susceptible katG ahpCF mutant strain from INH. Superoxide radicals, generated by paraquat, did not enhance the INH susceptibilities of wild-type cells. Hydrogen peroxide also potentiated the INH susceptibilities of susceptible and resistant (katG mutant) Mycobacterium smegmatis strains. Our results suggest that INH is converted to a more active drug by reaction with peroxides and that the INH susceptibilities of enterobacteria and mycobacteria are mechanistically related.
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PMID:Effects of peroxides on susceptibilities of Escherichia coli and Mycobacterium smegmatis to isoniazid. 798 15

Phagocytic cells respond to a variety of membrane stimulants by producing reactive oxygen intermediates (ROI), i.e. O2-, H2O2 and OH.metabolites. Plasma membrane activation is associated with superoxide generating NADPH oxidase, thereby causing the production of these toxic species. Stimulation of phagocytic cells also results in activation of purine catabolism, which directs the metabolic flux through xanthine oxidase to produce the superoxide anion. We previously observed that BL/LL macrophages (M phi) exhibited a premature inability to undergo tuftsin stimulated phagocytosis and microbicidal activity. The present study was undertaken to measure ROI levels in the absence and presence of 'tuftsin' pulsing as a function of in vitro culture age and also correlated these levels with adenosine deaminase (ADA) activity. The latter is known to be a contributor of O2- generation and is also involved in the maturation of the monocyte/macrophage system. The behaviour of normal and tuberculoid monocytes/macrophages were more or less the same, either in the presence or absence of tuftsin, i.e. they showed a progressive increase in ROI production until day 3, then tapered off in older cultures by day 7. In contrast, after day 1, the lepromatous macrophages were unable to undergo tuftsin mediated stimulation for the production of ROI and ADA activity. These findings indicate a defective M phi function in lepromatous patients towards tuftsin pulsing, thereby supporting our earlier observations. Thus BL/LL M phi behaved as if they were aged after 1 day of in vitro culture, which may account for an inability to handle Mycobacterium leprae for efficient killing.
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PMID:Modulation of peripheral blood derived monocytes/macrophages from leprosy patients using 'tuftsin' for production of reactive oxygen intermediates. 823


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