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)

Xanthine oxidase with acetaldehyde as substrate (the XOA system) generated superoxide anion and hydrogen peroxide, but this system had only weak bactericidal activity. Addition of Fe2+ and EDTA to the XOA system (XOA-Fe-EDTA system) increased bactericidal activity against Staphylococcus aureus, Escherichia coli, Listeria monocytogenes and Salmonella typhimurium, although both Mycobacterium tuberculosis and Candida albicans remained highly resistant. Catalase (H2O2 scavenger) and mannitol (.OH scavenger) almost completely inhibited the bactericidal activity of the XOA-Fe-EDTA system whereas SOD (O2- scavenger) was less inhibitory. Azide (1O2 scavenger) caused no such inhibition. The results suggest the possible role of .OH, H2O2 and O2- in the XOA-Fe-EDTA-mediated antimicrobial system, as effector molecules. There was no correlation between resistance of a given bacterium to active oxygen and the level of endogenous active oxygen-scavengers.
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PMID:Susceptibility of micro-organisms to active oxygen species: sensitivity to the xanthine-oxidase-mediated antimicrobial system. 312 35

Superoxide dismutase (EC 1.15.1.1) (SOD) activity has been detected in crude cell extracts of representative strains of the Mycobacterium avium, M. intracellulare, and M. scrofulaceum (MAIS) group. Polyacrylamide gel electrophoresis demonstrated a single SOD activity band for each of the MAIS strains, though there were differences in mobility. All M. avium and M. intracellulare and two of five M. scrofulaceum strains demonstrated a single activity band of identical mobility (Rf = 0.83), while the SOD activity band for the three remaining M. scrofulaceum strains migrated farther (Rf = 0.85). The differences in mobility correlated with differences in sensitivity to NaN3 and H2O2. The SOD activities of the majority of the MAIS strains which displayed the slower-migrating activity band were inhibited 22 to 81% after 15 min of exposure to 5 mM H2O2, suggesting that both iron and manganese may be present in a single enzyme. The SOD activities of the three M. scrofulaceum strains which had the faster-migrating activity band were inhibited 100% after only 5 min of exposure to 5 mM H2O2 and exhibited greater sensitivity to 5 and 10 mM NaN3, characteristics of an iron-containing SOD. A concentration of 1 mM KCN did not cause inhibition of enzyme activity in any of the MAIS strains tested. Extracellular SOD activity was detected in four of six MAIS strains and was shown to be identical in mobility to the SOD activity of the crude extracts.
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PMID:Superoxide dismutase activity of Mycobacterium avium, M. intracellulare, and M. scrofulaceum. 374 55

Adjuvant arthritis was induced in rats by the injection of Mycobacterium tuberculosis, and its severity was scored according to the macroscopic findings of the legs, tail, and ears. The average score so obtained was lower in SOD-injected rats than in the control group. The depression of albumin/globulin ratio was inhibited significantly in rats treated with 10.0 mg/kg of SOD. The levels of acid phosphatase and beta-glucuronidase were elevated after the administration of an adjuvant, and these lysosomal enzymes showed a remarkable increase in the control rats, while the elevation was inhibited in rats injected with 10.0 mg/kg of SOD. The levels of TBA-reactive substances in the sera and synovia were elevated at 2 weeks after the injection of adjuvant and decreased thereafter. In rats injected with 5.0 mg/kg or 10.0 mg/kg of SOD, the increase in both serum and synovial levels of TBA reactants was inhibited significantly. These observations suggest that the aggravation of adjuvant arthritis may be associated with lipid peroxidation due to superoxide, and that SOD may be beneficial for the treatment of arthritis.
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PMID:The increase of lipid peroxidation in rat adjuvant arthritis and its inhibition by superoxide dismutase. 401 32

A unique form of superoxide dismutase was isolated and characterized from Nocardia asteroides GUH-2. This enzyme contains 1 to 2 g atoms each of Fe, Mn, and Zn per mol and exhibits spectral properties suggestive of Fe- or Mn-containing superoxide dismutases. Its Mr = 100,000, and it is composed of four subunits of equal size which are not covalently joined. The amino acid composition of the enzyme was more closely related to the Mn- or Fe-containing enzymes of Mycobacterium species and was least related to the Cu-Zn enzyme of eukaryotes. Azide at 1 and 20 mM inhibits the activity 10 and 41%, respectively, and 5 mM H2O2 inhibits 40%, but 1 or 5 mM cyanide caused trivial effect. The immunofluorescent staining, which was specific for superoxide dismutase of N. asteroides, indicated the association of this enzyme to the outer cell wall of the organism. Further, the enzyme was shown to be selectively secreted into the medium.
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PMID:Purification and properties of a unique superoxide dismutase from Nocardia asteroides. 633 58

The X-ray structure of the tetrameric iron-dependent superoxide dismutase from Mycobacterium tuberculosis has been refined to an R-factor of 0.167 and a correlation coefficient of 0.954 at 2.0 A resolution. The crystals are monoclinic P2(1) and have four subunits related by strong non-crystallographic 222 (or D2) symmetry in the asymmetric unit. 198 of the 207 amino acids of each subunit are defined by the electron density which shows that they adopt the conserved fold of other iron- or manganese-dependent SODs. The structure can be divided into two domains, the N-terminal domain involving an extended region followed by two projecting antiparallel alpha-helices, and the C-terminal domain containing four more helical segments with a three-stranded antiparallel beta-sheet inserted sequentially between the fourth and fifth helices. The catalytic iron is co-ordinated by five ligands: three histidines (residues 28, 76 and 164), one aspartate (160) and a solvent molecule. The inferred positions of protons at the active site are consistent with the solvent ligand being a hydroxide ion. This ligand interacts with His145 in the Mycobacterium tuberculosis SOD. In the highly homologous Mycobacterium leprae Mn-SOD, the histidine is replaced by glutamine, this being the only significant residue difference within 10 A of the Fe3+. The nature of the amino acid at this position may influence the metal ion specificity of these enzymes. The subunits of the Mycobacterium tuberculosis SOD associate by polar contacts to form dimers, which closely resemble those of other dimeric or tetrameric Fe- or Mn-SODs. However, the dimer-dimer interactions within the tetramer are novel, being dominated by dimerisation of the 144 to 152 loop regions which connect the outer two beta-strands of the three-membered beta-sheet. This contrasts strongly with the other tetrameric Fe- or Mn-SODs where the dimer-dimer association is dominated by the projecting alpha alpha-turn in the N-terminal domain.
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PMID:X-ray structure analysis of the iron-dependent superoxide dismutase from Mycobacterium tuberculosis at 2.0 Angstroms resolution reveals novel dimer-dimer interactions. 787 74

We have refined the X-ray structure of a site-directed G152A mutant of the iron-dependent superoxide dismutase from Mycobacterium tuberculosis at 2.9 angstroms resolution. The mutation which replaces a glycine residue in a surface loop with alanine was designed to alter the conformation of this loop region which has previously been shown to play a crucial structural role in quaternary interactions within the SOD tetramer. Gly-152 was targeted as it has dihedral angles (phi = 83.1 degrees, psi = -0.3 degrees) close to the left-handed alpha-helical conformation which is rarely adopted by other amino acids except asparagine. Gly-152 was replaced by alanine as it has similar size and polarity, yet has a very low tendency to adopt similar conformations. X-ray data collection on crystals of this mutant at 2.9 angstroms resolution and subsequent least-squares refinement to an R-value of 0.169 clearly establish that the loop conformation is unaffected. Fluorescence studies of guanidine hydrochloride denaturation establish that the mutant is 4 kcal/mol less stable than the wild-type enzyme. Our results indicate that strict conformational constraints imposed upon a region of polypeptide, due for example to interactions with a neighbouring subunit, may force an alanine residue to adopt this sterically hindered conformation with a consequent reduction in stability of the folded conformation.
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PMID:X-ray structure analysis of an engineered Fe-superoxide dismutase Gly-Ala mutant with significantly reduced stability to denaturant. 867 28

Mycobacterium avium is an intracellular pathogen capable of growing inside the phagosomal compartment of macrophages. In this work, we characterized the superoxide dismutase of M. avium, as a putative candidate to resist the oxidative stress. The gene sodA encoding superoxide dismutase (SOD:EC1.15.1.1) from Mycobacterium avium TMC724 was cloned and sequenced. It encodes a 23 kDa protein (207 aminoacids) showing identity with the Mycobacterium leprae SOD (91%) and the M. tuberculosis SOD (83%). This enzyme was functionally expressed in both Escherichia coli and Mycobacterium smegmatis, and identified as a manganese (Mn) SOD on the basis of sequence comparison with other MnSODs from different organisms, and by activity inhibition studies. By indirect immunogold labeling of M. avium with a mAb directed against M. leprae SOD, the enzyme was found to be exposed at the cell surface of M. avium. It was also shown that SOD was released in supernates of M. avium TMV724 during exponential growth, suggesting a role of this enzyme during interactions with the environment. When SOD was expressed in the non-pathogenic M. smegmatis, it was also exposed at the surface of bacteria and released in supernates, but this was not sufficient to protect this recombinant mycobacterium from the killing mechanisms of macrophages.
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PMID:Molecular characterization of a surface-exposed superoxide dismutase of Mycobacterium avium. 869 9

The production of reactive nitrogen intermediates (RNI) by macrophages is critical to host defence, particularly for exerting the bactericidal and tumoricidal properties. Nitric oxide (NO) were measured in the peripheral blood-derived monocytes/macrophages of normal and leprosy patients (BT/TT and BL/LL) in the presence and absence of 'tuftsin' as a function of in vitro culture age (on 1, 3, 7 days). Macrophages from both groups of leprosy patients were able to produce NO during the unstimulated state but only BL/LL macrophages could be activated by tuftsin to produce significantly high levels of NO. This increase was highest on day 1, then gradually decreased with in vitro culture age. Surprisingly, tuftsin was unable to enhance the NO production in normal macrophages above the basal level. Further, normal and BT/TT macrophages had only Cu-Zn derived superoxide dismutase (SOD) activity whereas BL/LL cultures has Cu-Zn and Mn derived SOD activity. These studies indicate that in BL/LL cultures: a, apart from tuftsin, some additional signal is required to activate nitric oxide synthase (NOS) gene for NO production; and b, Mn-SOD produced by Mycobacterium leprae is playing a defensive role against toxic-free radicals. The final outcome of this mechanism is the survival of M. leprae inside the macrophages.
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PMID:Release of reactive nitrogen intermediates from the peripheral blood-derived monocytes/macrophages of leprosy patients stimulated in vitro by tuftsin. 912 27

We evaluated the performance of an automatic polymerase chain reaction (PCR) detection system for identification of Mycobacterium tuberculosis in respiratory specimens. Six hundred and two respiratory specimens, including 557 sputa and 45 bronchial washing samples, were analyzed using the COBAS AMPLICOR Mycobacterium tuberculosis (MTB) test. The results were compared with those obtained from acid-fast microscopy, conventional culture, and clinical history. In cases of discrepancy between the results of the COBAS AMPLICOR MTB test and culture, the medical history of the patient was reviewed, the COBAS AMPLICOR MTB test was repeated, and the gene encoding M. tuberculosis superoxide dismutase was screened using PCR (SOD-PCR). Fourteen samples were excluded because the internal control test result was negative. Of 57 specimens that were culture positive for Mycobacterium species, 40 appeared to have growth of M. tuberculosis and 21 were smear positive for acid-fast bacteria. The sensitivity, specificity, and positive and negative predictive values for the COBAS AMPLICOR MTB test evaluated at our laboratory were 85.0% (34/40), 99.3% (544/548), 89.5% (34/38), and 98.9% (544/550), respectively. Three specimens that were culture positive for M. tuberculosis but negative by COBAS AMPLICOR MTB test were positive when rechecked by both COBAS AMPLICOR MTB test and SOD-PCR. Among the four specimens with positive reactions on both COBAS AMPLICOR MTB test and SOD-PCR that were culture negative, two were from patients who had been receiving antituberculosis treatment, one was from a patient who had been treated for tuberculosis for 1 year, and the other was from a patient who died of sepsis with adult respiratory distress syndrome. In more than 70% of smear-negative and culture-positive specimens and 86.4% of smear-positive specimens, M. tuberculosis was identified by the COBAS AMPLICOR MTB test within 10 hours after receipt of the specimens. Our data show that the COBAS AMPLICOR MTB test provides rapid and accurate detection of M. tuberculosis in respiratory specimens.
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PMID:Evaluation of an automatic polymerase chain reaction assay for identification of Mycobacterium tuberculosis in respiratory specimens. 954 72

Mycothione reductase from the human pathogen Mycobacterium tuberculosis has been cloned, expressed in Mycobacterium smegmatis, and purified 145-fold to homogeneity in 43% yield. Amino acid sequence alignment of mycothione reductase with the functionally homologous glutathione and trypanothione reductase indicates conservation of the catalytically important redox-active disulfide, histidine-glutamate ion pair, and regions involved in binding both the FAD cofactor and the substrate NADPH. The homogeneous 50 kDa subunit enzyme exists as a homodimer and is NADPH-dependent and highly specific for the structurally unique low-molecular mass disulfide, mycothione, exhibiting Michaelis constants of 8 and 73 microM for NADPH and mycothione, respectively. HPLC analysis indicated the presence of 1 mol of bound FAD per monomer as the cofactor exhibiting an absorption spectrum with a lambda(max) at 462 nm with an extinction coefficient of 11 300 M(-)(1) cm(-)(1). The reductive titration of the enzyme with NADH indicates the presence of a charge-transfer complex of one of the presumptive catalytic thiolates and FAD absorbing at ca. 530 nm. Reaction with serially truncated mycothione and other disulfides and pyridine nucleotide analogues indicates a strict minimal disulfide substrate requirement for the glucosamine moiety of mycothione. The enzyme exhibits bi-bi ping-pong kinetics with both disulfide and quinone substrates. Transhydrogenase activity is observed using NADH and thio-NADP(+), confirming the kinetic mechanism. We suggest mycothione reductase as the newest member of the class I flavoprotein disulfide reductase family of oxidoreductases.
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PMID:Expression, purification, and characterization of Mycobacterium tuberculosis mycothione reductase. 1051 39


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