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)

A 33 year old male Nigerian presented with widespread involvement of peripheral nerves, several of which were tender and painful. Nerve biopsies confirmed the presence of Mycobacterium leprae in both endoneurial and perineurial areas, mainly in foamy macrophages (Virchow cells), but there were also large accumulations of an amorphous, acid-fast and alcohol-fast material which was not obviously of bacterial origin. Appropriate stains indicated that this had many characteristics of lipofuscin. Although not previously known, it was at this stage discovered that the patient had received treatment with anti-leprosy drugs nearly three years before presentation in this country. One of these was clofazimine, an aniline aposafranine derivative known to produce a ceroid-like pigment in the tissues of patients treated with this drug or lepromatous leprosy.
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PMID:Intra-neural ceroid-like pigment following the treatment of lepromatous leprosy with clofazimine (B663; Lamprene). 626 Sep

Sixty CBA mice were intravenously inoculated with the Mycobacterium tuberculosis (MBT) strains Erdman and 2255 (a polyresistant clinical strain) pretreated with dissolved ozone (experimental groups), a single therapeutical dose. of dissolved ozone being intravenously injected. By 1 month of inoculation, all control mice (MBT-inoculated and ozone-untreated) died and in their organs there were a great deal of MBT both outside and inside the macrophages. No pathogen in its typical form was not found in experimental mice, but there were many granular and L forms, the lung showing a large number of highly vacuolized (foamy) alveolar macrophages (AM). All experimental mice survived by month 5 and their organ examination showed that the pathogen was detectable only inside the macrophages, but they are chiefly unchanged (more elongated and badly stained with aniline dyes). Juvenile forms are prevalent among AM. It should be concluded that the action of dissolved ozone on AM and MBT is heterodirectional.
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PMID:[Action of dissolved ozone on mycobacterium tuberculosis and alveolar macrophages in experimental tuberculosis]. 916 32

Arylamine N-acetyltransferases (NATs) are found in many eukaryotic organisms, including humans, and have previously been identified in the prokaryote Salmonella typhimurium. NATs from many sources acetylate the antitubercular drug isoniazid and so inactivate it. nat genes were cloned from Mycobacterium smegmatis and Mycobacterium tuberculosis, and expressed in Escherichia coli and M. smegmatis. The induced M. smegmatis NAT catalyzes the acetylation of isoniazid. A monospecific antiserum raised against pure NAT from S. typhimurium recognizes NAT from M. smegmatis and cross-reacts with recombinant NAT from M. tuberculosis. Overexpression of mycobacterial nat genes in E. coli results in predominantly insoluble recombinant protein; however, with M. smegmatis as the host using the vector pACE-1, NAT proteins from M. tuberculosis and M. smegmatis are soluble. M. smegmatis transformants induced to express the M. tuberculosis nat gene in culture demonstrated a threefold higher resistance to isoniazid. We propose that NAT in mycobacteria could have a role in acetylating, and hence inactivating, isoniazid.
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PMID:Cloning and characterization of arylamine N-acetyltransferase genes from Mycobacterium smegmatis and Mycobacterium tuberculosis: increased expression results in isoniazid resistance. 997 65

Arylamine N:-acetyltransferase (NAT) was first identified as the inactivator of the anti-tubercular drug isoniazid. The enzyme was shown to catalyse the transfer of an acetyl group from acetyl-CoA to the terminal nitrogen of the hydrazine drug. The rate of inactivation of isoniazid was polymorphically distributed in the population and was one of the first examples of pharmacogenetic variation. NAT was identified recently in Mycobacterium tuberculosis and is a candidate for modulating the response to isoniazid. Genome sequences have revealed many homologous members of this unique family of enzymes. The first three-dimensional structure of a member of the NAT family identifies a catalytic triad consisting of aspartate, histidine and cysteine proposed to form the activation mechanism. So far, all procaryotic NATs resemble the human enzyme which acetylates isoniazid (NAT2). Human NAT2 is characteristic of drug-metabolizing enzymes: it is found in liver and intestine. In humans and other mammals, there are up to three different isoenzymes. If only one isoenzyme is present, it is like human NAT1. Human NAT1 and its murine equivalent specifically acetylate the folate catabolite p-aminobenzoylglutamate. NAT1 and its murine homologue each have a ubiquitous tissue distribution and are expressed early in development at the blastocyst stage. During murine embryonic development, NAT is expressed in the developing neural tube. The proposed endogenous role of NAT in folate metabolism, and its multi-allelic nature, indicate that its role in development should be assessed further.
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PMID:An update on genetic, structural and functional studies of arylamine N-acetyltransferases in eucaryotes and procaryotes. 1100 99

Arylamine N-acetyltransferases (NATs) catalyse the transfer of an acetyl group from acetyl CoA to the terminal nitrogen of hydrazine and arylamine drugs and carcinogens. These enzymes are polymorphic and have an important place in the history of pharmacogenetics, being first identified as responsible for the polymorphic inactivation of the anti-tubercular drug isoniazid. NAT has recently been identified within Mycobacterium tuberculosis itself and is an important candidate for modulating the response of mycobacteria to isoniazid. The first three-dimensional structure of the unique NAT family shows the active-site cysteine to be aligned with conserved histidine and aspartate residues to form a catalytic triad, thus providing an activation mechanism for transfer of the acetyl group from acetyl CoA to cysteine. The unique fold could allow different members of the NAT family to play a variety of roles in endogenous and xenobiotic metabolism.
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PMID:Arylamine N-acetyltransferases - of mice, men and microorganisms. 1123 77

Arylamine N-acetyltransferases (NATs; E.C 2.3.1.5) N-acetylate arylhydralazine and arylamine substrates using acetyl coenzyme A. Human NAT2 acetylates and inactivates the antituberculosis drug, isoniazid (INH), and is polymorphic. We previously demonstrated that there is a homologue of human NAT2 in Mycobacterium tuberculosis, whose product N-acetylates INH in vitro. We now demonstrate that the nat gene is expressed in M. tuberculosis and M. bovis Bacille Calmette-Guerin (BCG), using reverse transcription-polymerase chain reaction and Western blotting. The NAT protein is active in M. bovis BCG in vivo, as detected by the presence of N-acetyl INH in M. bovis BCG lysates grown in INH. Sequence analysis of the M. tuberculosis nat coding region reveals a single nucleotide polymorphism in 18% of a random cohort of M. tuberculosis clinical isolates, conferring a G to R change. The recombinant mutant protein appears less stable than the wild type, and has an apparent affinity for INH of 10-fold less than the wild type. Modelling the change in M. tuberculosis NAT shows that the G to R change is close to the active site, and supports the experimental findings. Minimum inhibitory concentration data suggest that this polymorphism in nat is linked to low-level changes in the INH susceptibility of M. tuberculosis clinical isolates.
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PMID:Arylamine N-acetyltransferase of Mycobacterium tuberculosis is a polymorphic enzyme and a site of isoniazid metabolism. 1170 56

Arylamine N-acetyltransferases (NATs) catalyze the transfer of an acetyl group from acetyl-CoA to arylhydrazines and to arylamine drugs and carcinogens or to their N-hydroxylated metabolites. NAT plays an important role in detoxification and metabolic activation of xenobiotics and was first identified as the enzyme responsible for inactivation of the antitubercular drug isoniazid, an arylhydrazine. The rate of inactivation was polymorphically distributed in the population: the first example of interindividual pharmacogenetic variation. Polymorphism in NAT activity is primarily due to single nucleotide polymorphisms (SNPs) in the coding region of NAT genes. NAT enzymes are widely distributed in eukaryotes and genome sequences have revealed many homologous members of this enzyme family in prokaryotes. The structures of S almonella typhimurium and Mycobacterium smegmatis NATs have been determined, revealing a unique fold in which a catalytic triad (Cys-His-Asp) forms the active site. Determination of prokaryotic and eukaryotic NAT structures could lead to a better understanding of their role in xenobiotics and endogenous metabolism.
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PMID:The pharmacogenetics of NAT: structural aspects. 1196

Arylamine N-acetyltransferases which acetylate and inactivate isoniazid, an anti-tubercular drug, are found in mycobacteria including Mycobacterium smegmatis and Mycobacterium tuberculosis. We have solved the structure of arylamine N-acetyltransferase from M. smegmatis at a resolution of 1.7 A as a model for the highly homologous NAT from M. tuberculosis. The fold closely resembles that of NAT from Salmonella typhimurium, with a common catalytic triad and domain structure that is similar to certain cysteine proteases. The detailed geometry of the catalytic triad is typical of enzymes which use primary alcohols or thiols as activated nucleophiles. Thermal mobility and structural variations identify parts of NAT which might undergo conformational changes during catalysis. Sequence conservation among eubacterial NATs is restricted to structural residues of the protein core, as well as the active site and a hinge that connects the first two domains of the NAT structure. The structure of M. smegmatis NAT provides a template for modelling the structure of the M. tuberculosis enzyme and for structure-based ligand design as an approach to designing anti-TB drugs.
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PMID:The structure of arylamine N-acetyltransferase from Mycobacterium smegmatis--an enzyme which inactivates the anti-tubercular drug, isoniazid. 1205 3

Arylamine N-acetyltransferases (NATs) catalyse the acetylation of arylamine, arylhydrazine and arylhydroxylamine substrates by acetyl Coenzyme A. NAT has been discovered in a wide range of eukaryotic and prokaryotic species. Although prokaryotic NATs have been implicated in xenobiotic metabolism, to date no endogenous role has been identified for the arylamine N-acetyl transfer reaction in prokaryotes. Investigating the substrate specificity of these enzymes is one approach to determining a possible endogenous role for prokaryotic NATs. We describe an accurate and efficient assay for NAT activity that is suitable for high-throughput screening of potential NAT ligands. This assay has been utilised to identify novel substrates for pure NAT from Salmonella typhimurium and Mycobacterium smegmatis which show a relationship between the lipophilicity of the arylamine and its activity as a substrate. The lipophilic structure/activity relationship observed is proposed to depend on the topology of the active site using docking studies of the crystal structures of these NAT isoenzymes. The evidence suggests an endogenous role of NAT in the protection of bacteria from aromatic and lipophilic toxins.
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PMID:An approach to identifying novel substrates of bacterial arylamine N-acetyltransferases. 1262 50

Grecz, Nicholas (University of Chicago, Chicago, Ill.), and Gail M. Dack. Taxonomically significant color reactions of Brevibacterium linens. J. Bacteriol. 82:241-246. 1961.-Brevibacterium linens was observed to give characteristic color reactions with certain bases and acids. An intensive carmine-red color appeared immediately after addition of a drop of 5 n sodium hydroxide, 5 n potassium hydroxide, and saturated barium hydroxide. A light carmine-red was given by lithium hydroxide, and a light orange-red with a milky suspension of calcium hydroxide. No discernible color change was given with weak bases such as ammonium hydroxide, aniline, and pyridine.A characteristic salmon-pink color was produced when B. linens was rubbed with a glass rod in a drop of glacial acetic acid or filter paper; a brick-red color was produced with aniline under these conditions. With syrupy phosphoric acid a green color appeared within 3 to 4 min which turned blue after approximately 3 hr. The blue color was stable for several days. On the basis of these color reactions, B. linens could be distinguished from other microorganisms possessing yellow-orange pigmentation, i.e., Staphylococcus aureus, Staphylococcus epidermidis, Micrococcus flavus, Micrococcus citreus, Mycobacterium phlei, Sarcina lutea. Therefore, these color changes may be used for the identification of B. linens. Original isolates of B. linens from cheese were tested by these spot reactions and all presumptive identifications could be subsequently confirmed by conventional methods. Blue and green colors appeared in all yellow-orange chromogens treated with sulfuric, perchloric, and hydrochloric acids and hence these colors were not specific for B. linens.
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PMID:Taxonomically significant color reactions of Brevibacterium linens. 1370 47


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