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)

In vitro sensitivities to various drugs of a total of 106 strains of atypical mycobacteria were studied in modified Dubos Tween albumin liquid medium. Eight triple-drug combinations of antituberculous drugs were also evaluated in vitro for their potentiated activities. Minimal to moderate potentiation was demonstrated in the majority of the combination. From the results, the triple-drug combination--including rifampin, one of three aminoglycosides (streptomycin, kanamycin, viomycin), and either ethionamide or ethambutol--might be recommended for Mycobacterium kansasii infections. Against Mycobacterium avium-intracellulare infections, rifampin-kanamycin-ethionamide or rifampin-kanamycin-ethambutol might be the choice if we were to select any triple-drug regimen. None of the triple-drug regimens thus far tested on M. avium-intracellulare were active enough to recommend fully for clinical use. In vivo experimental chemotherapy of murine infection with Mycobacterium intracellulare (TMC 1469) on a five-drug regimen, kanamycin-rifampin-cycloserine-ethambutol-ethionamide, showed a moderate therapeutic effect but the infection was not eradicated.
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PMID:In vitro and in vivo susceptibility of atypical mycobacteria to various drugs. 733 20

A mild grade of liver damage in rabbits was produced by giving 23 subcutaneous injections of carbon tetrachloride (CCl4). The CCl4-treated rabbits and untreated controls were subsequently challenged with the mildly virulent strain of Mycobacterium avium Kirschberg (TMC 801). In two successive experiments it has been found that liver damage increased the susceptibility of rabbits to infection with this organism.
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PMID:Increased susceptibility of rabbits to intravenous challenge with Mycobacterium avium after mild hepatitis produced by carbon tetrachloride. 738 19

The Mycobacterium tuberculosis complex includes M. tuberculosis, M. bovis, M. microti, and M. africanum. Seven strains of the M. tuberculosis complex were sequenced in a region of about 300 bp which contains multiple 15-bp tandem repeats and which is part of a 1,551-bp open reading frame. Four distinct sequences were obtained, each defining a sequevar. A sequevar includes the strain or strains with a given sequence. The type strain M. tuberculosis TMC 102 (H37Rv) was designated sequevar MED-G. When compared to MED-G, sequevar LONG had an insertion of one 15-bp tandem repeat and sequevar SHORT had a deletion of one tandem repeat. Sequevar MED-C had a G-->C substitution, coding for the conservative change Ser-->Thr. BanI cuts only sequevar MED-C at the site of the substitution. PCR-restriction enzyme analysis was used to determine the sequevars of 92 M. tuberculosis complex strains. All 23 M. bovis BCG strains belonged to sequevar MED-C. The M. africanum type strain was sequevar SHORT. The remaining 68 strains of M. tuberculosis, M. bovis (not BCG), and M. microti were sequevars LONG (3 strains) or MED-G (65 strains). PCR-restriction enzyme analysis was applied to reference strains and clinical isolates with a worldwide distribution. This method provides rapid, sensitive, and specific identification of the important vaccine strain M. bovis BCG.
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PMID:Differentiation of strains in Mycobacterium tuberculosis complex by DNA sequence polymorphisms, including rapid identification of M. bovis BCG. 779 Apr 48

The ability of the host to resist infection to a variety of intracellular pathogens, including mycobacteria, is strongly dependent upon the expression of the Bcg gene. Mouse strains which express the resistance phenotype (Bcgr) restrict bacterial growth, whereas susceptible strains (Bcgs) allow bacterial growth. Expression of the Bcg allele is known to influence the priming of host macrophages (M phi s) for bactericidal function. In the present work, bone marrow-derived M phi s from congenic BALB/c (Bcgs) and C.D2 (BALB/c.Bcgr) mice were infected with the virulent strain Mycobacterium avium TMC 724 to define the mechanism involved in growth restriction of M. avium. By combining CFU measurements and ultrastructural analyses, we show that growth of this bacterium is restricted in marrow M phi s from resistant mice. Using acid phosphatase as a lysosomal marker, we provide evidence that the hydrolytic activity of M phi s, as measured by the capacity of lysosomes to fuse with and transfer active hydrolytic enzymes to phagosomes in which M. avium resides, is an expression of the Bcg gene and that this phenomenon is a key antibacterial activity responsible for growth restriction of M. avium: (i) the percentage of phagosome-lysosome fusions was twice as high in Bcgr M phi s as in Bcgs M phi s, and (ii) the percentage of intact viable bacteria residing in acid phosphatase-negative phagosomes was twice as low in Bcgr M phi s as in the Bcgs counterparts. These differences are not due to a lower activity of the enzyme in Bcgr M phi s. The mechanism by which the Bcg gene exerts control over the phagolysosomal fusion is discussed.
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PMID:Implication of phagosome-lysosome fusion in restriction of Mycobacterium avium growth in bone marrow macrophages from genetically resistant mice. 835 99

Previously, a gene cluster, termed ser2, which encodes for the synthesis of the specific oligosaccharide of the glycopeptidolipid antigen of Mycobacterium avium serovar 2 strain TMC 724, was defined. DNA probes from this cloned ser2 gene cluster have now been used to clone and characterize the ser2 region from a strain of M. avium which produces rough and smooth colony forms and to identify the genetic differences between these morphotypes. Interstrain differences were seen to exist between the ser2 gene cluster of M. avium strains TMC 724 and 2151. In addition, two distinct rough (Rg) genotypes of strain 2151 were defined by this analysis. The first of these, present in the M. avium Rg-0 and Rg-1 variants, was attributed to a deletion of approximately 28 kilobases from smooth variants, including the entire ser2 gene cluster. This particular deletion is thought to be mediated by recombination between repetitive sequences that flank both sides of the 28-kilobase excised region. The second genotype, seen in M. avium Rg-3 and Rg-4 variants, results from the deletion of an undefined amount of DNA from the right of the ser2 gene cluster. Reported separately (Belisle, J. T., McNeil, M. R., Chaterjee, D., Inamine, J. M., and Brennan, P. J. (1993) J. Biol. Chem. 268, 10510-10516) are the results of biochemical analyses of the glycopeptidolipid/lipopeptide population of the Rg genotypes which revealed that Rg-0 and Rg-1 possess lipopeptides devoid of all of the sugars of the glycopeptidolipids and are obviously biosynthetic precursors of the glycopeptidolipids. These studies help formulate a definition of the physiological effects of glycolipid expression, the biosynthetic and genetic mechanisms involved in their formation, and toward an understanding of the role of M. avium as a serious opportunistic pathogen.
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PMID:Rough morphological variants of Mycobacterium avium. Characterization of genomic deletions resulting in the loss of glycopeptidolipid expression. 848 4

Mycobacterium "habana" strain TMC 5135, which has been proposed as a vaccine against both leprosy and tuberculosis, is considered to be a strain of serotype I of the recognized species Mycobacterium simiae. We have now shown that each of these strains possesses characteristic polar glycopeptidolipids (GPL) which are sufficiently different to allow unequivocal strain identification. Thin layer chromatographic analysis demonstrated that M. habana synthesizes a family of apolar GPLs and three distinct polar GPLs (pGPL-I to -III) which exhibited migration patterns different from those of M. simiae serotype I (pGPL-Sim). Using a combination of chemical, mass spectrometric, and proton-NMR analyses, the GPLs from M. habana were determined to be based on the same generic structure as those from the M. avium complex, namely N-fatty acyl-D-Phe-(O-saccharide)-D-allo-Thr-D-Ala-L-alaninyl-O-m onosaccharide. The de-O-acetylated apolar GPLs contain a 3-O-Me-6-deoxy-Tal attached to the allo-Thr and either a 3-O-Me-Rha or a 3,4-di-O-Me-Rha attached to the alaninol. In the pGPLs, oligosaccharides were found to be attached to the allo-Thr. The oligoglycosyl alditol reductively released from the least polar pGPL-I was fully characterized as L-Fucp alpha 1 in --7 with 3-(6-O-Me)-D-Glcp beta 1 in --7 with 3-(4-O-Me)-L-Rhap alpha 1 in --7 with 3-L-Rhap alpha 1 in --7 with 2-(3-O-Me)-6-deoxy-Tal. In pGPl-II and -III, the terminal Fuc residue is further 3-O-methylated and 4-O-substituted with an additional 2,4-di-O-Me-D-GlcA and 4-O-Me-D-GlcA, respectively. The corresponding oligosaccharide from pGPL-Sim was shown to be of identical molecular weight to pGPL-II but terminating with a 3,4-di-O-Me-GlcA. Enzyme-linked immunosorbent assay-based serological studies using anti-M. habana and anti-M. simiae sera against whole cells and purified pGPLs firmly established the polar GPLs as important antigens and indicated that the terminal epitopes L-Fuc-, 2,4-di-O-Me-D-GlcA, and 4-O-Me-D-GlcA uniquely present in pGPL-I, -II, and -III, respectively, confer sufficient specificity for the identification of M. habana as a distinct serotype of M. simiae.
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PMID:Novel O-methylated terminal glucuronic acid characterizes the polar glycopeptidolipids of Mycobacterium habana strain TMC 5135. 864 35

This study describes the purification and immunochemical characterization of a major 23 kDa cytosolic protein antigen of the vaccine candidate Mycobacterium habana (TMC 5135). The 23 kDa protein alone was salted out from the cytosol at an ammonium sulfate saturation of 80-95%. It represented about 1.5% of the total cytosolic protein, appeared glycosylated by staining with periodic acid/Schiff's reagent, and showed a pl of approximately 5.3. Its native molecular mass was determined as approximately 48 kDa, suggesting a homodimeric configuration. Immunoblotting with the WHO-IMMLEP/IMMTUB mAbs mc5041 and IT61 and activity staining after native PAGE established its identity as a mycobacterial superoxide dismutase (SOD) of the Fe/Mn type. The sequence of the 18 N-terminal amino acids, which also contained the binding site for mc5041, showed a close resemblance, not only with the reported deduced sequences of Mycobacterium leprae and Mycobacterium tuberculosis Fe/MnSODs, but also with human MnSOD. In order to study its immunopathological relevance, the protein was subjected to in vivo and in vitro assays for T cell activation. It induced, in a dose-related manner, skin delayed hypersensitivity in guinea-pigs and lymphocyte proliferation in BALB/c mice primed with M. habana. Most significantly, it also induced lymphocyte proliferative responses, in a manner analogous to M. Ieprae, in human subjects comprising tuberculoid leprosy patients and healthy contacts.
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PMID:A major T-cell-inducing cytosolic 23 kDa protein antigen of the vaccine candidate Mycobacterium habana is superoxide dismutase. 870 77

Infection with the virulent Mycobacterium avium strain TMC 724 caused progressive infection in C57BL/6 and BALB/c mice, while infection with a less virulent strain (M. avium SE 01) resulted in chronically persistent bacterial loads. Livers of mice infected with TMC 724 were characterized by progressively expanding tumor-like infiltrations of epithelioid macrophages, while SE 01 induced well-developed, compact epithelioid granulomas that remained constant in size and number for at least 4 months. When C57BL/6 mice were depleted of CD4+ T cells by i.p. administration of specific mAb at the time of infection, their capacity to initiate granuloma formation was completely abrogated during the first 4 weeks of infection. Semi-quantitative competitive RT-PCR of liver homogenates obtained 3 weeks after infection revealed that depletion of CD4+ T cells was accompanied by a 25-fold reduced expression of IFN-gamma mRNA and a 5-fold reduced expression of tumor necrosis factor (TNF)-alpha mRNA when compared to control infected mice. Granuloma morphology in response to either TMC 724 or SE 01 was similar in immunodeficient SCID mice to that observed in syngeneic BALB/c mice. However, SCID mice developed granulomas in a delayed fashion and were less efficient in surrounding infected Kupffer cells with an inflammatory infiltration. The delayed kinetics of granuloma initiation in infected SCID mice was paralleled by a lower mRNA expression for IFN-gamma and TNF-alpha compared to that observed in infected BALB/c mice. mAb-mediated neutralization of IFN-gamma in BALB/c mice significantly reduced inflammatory infiltrations and granuloma formation. These data support the conclusion that CD4+ T cells accelerate granuloma formation by enhancing the production of TNF-alpha and IFN-gamma at the site of infection.
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PMID:Mechanisms of granuloma formation in murine Mycobacterium avium infection: the contribution of CD4+ T cells. 891 99

Murine bone marrow-derived macrophages (Mphis) infected with virulent strains of Mycobacterium avium (TMC 724 and a human clinical isolate) or with an avirulent opaque variant that spontaneously dissociates from the virulent human clinical isolate were subjected to a prolonged and continuous treatment with clarithromycin added at the MIC. The efficiency of this antibiotic in terms of inhibition of bacterial growth and bacterial degradation was evaluated during a 21-day treatment period. Growth was assessed by determination of CFU of intracellular bacteria and by a quantitative ultrastructural analysis which allowed us also to determine the extent of bacterial degradation. A similar treatment was applied to the same strains growing in liquid medium. Our data show that in liquid medium, clarithromycin caused a 90% decrease in CFU within 7 days of treatment. When applied to Mphis infected with virulent M. avium, clarithromycin immediately arrested bacterial growth but was unable to fully kill and degrade intracellularly growing virulent bacteria. After 21 days of treatment, 25% of intracellular bacteria were still morphologically intact. These bacteria resumed growth upon removal of the antibiotic, with a normal replication rate. These bacteria had not become more resistant to the drug, since the MIC was unchanged as compared to the one determined for the initial stock used to infect Mphis. Our data therefore suggest that the intraphagosomal environment protects bacteria from degradation. We propose that the inability of the drug to completely destroy bacteria is the result of a limited accessibility of the drug due to prevention of fusions between the immature phagosomes in which virulent bacteria reside and lysosomes in which clarithromycin accumulates. In accord with our proposal, we show that the avirulent opaque variant, which does not prevent phagosome-lysosome fusions (unpublished data), is finally destroyed by clarithromycin even within the phagosomal environment.
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PMID:The phagosomal environment protects virulent Mycobacterium avium from killing and destruction by clarithromycin. 919 52

Fatty and mycolic acids and the pattern of glycolipids were studied in a collection of 34 strains of 'Mycobacterium habana' and in two strains of Mycobacterium simiae. Major glycolipids of these micro-organisms were assigned to the glycopeptidolipid (GPL) structural type, but both mycobacteria differed in the patterns obtained by TLC. The strains of 'M. habana' were separated into four groups (A-D), taking into account the presence or absence of several polar GPLs: group A contained GPL-I, GPL-II and GPL-III; group B contained GPL-I, GPL-II', GPL-II and GPL-III; group C contained GPL-II', GPL-II and GPL-III; group D did not contain any of these compounds. Fatty acids of both bacteria were similar, and ranged from 14 to 26 carbon atoms, hexadecanoic, octadecenoic and tuberculostearic acids being predominant. Mycolic acids were also similar by TLC and HPLC, and consisted of alpha-, alpha'- and ketomycolates. Partial structural analysis by MS carried out in strains 'M. habana' TMC 5135 and M. simiae ATCC 25275T revealed that alpha- and ketomycolates ranged, in general, from 79 to 87 carbon atoms, and alpha'-mycolates from 58 to 67 carbon atoms. The alpha- and ketomycolates belonged to several structural series, and minor variations were found between the two strain examined. The data obtained justified the synonymy between 'M. habana' and M. simiae but indicated, in turn, that the former can be distinguished on the basis of GPL analysis. Most strains of 'M. habana' can be defined by the presence of GPL-II and GPL-III, a finding that could be useful in the quality control of potential vaccine strains.
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PMID:Analysis of lipids reveals differences between 'Mycobacterium habana' and Mycobacterium simiae. 961 92


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