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  • 1
    Online Resource
    Online Resource
    Different Strains of Mycobacterium tuberculosis Cause Various Spectrums of Disease in the Rabbit Model of Tuberculosis
    American Society for Microbiology ; 2003
    In:  Infection and Immunity Vol. 71, No. 10 ( 2003-10), p. 6004-6011
    Details
    In: Infection and Immunity, American Society for Microbiology, Vol. 71, No. 10 ( 2003-10), p. 6004-6011
    Abstract: The rabbit model of tuberculosis has been used historically to differentiate between Mycobacterium tuberculosis and Mycobacterium bovis based on their relative virulence in this animal host. M. tuberculosis infection in market rabbits is cleared over time, whereas infection with M. bovis results in chronic, progressive, cavitary disease leading to death. Because of the innate resistance of commercial rabbits to M. tuberculosis , 320 to 1,890 log-phase, actively growing inhaled bacilli were required to form one grossly visible pulmonary tubercle at 5 weeks. The range of inhaled doses required to make one tubercle allows us to determine the relative pathogenicities of different strains. Fewer inhaled organisms of the M. tuberculosis Erdman strain were required than of M. tuberculosis H37Rv to produce a visible lesion at 5 weeks. Furthermore, with the Erdman strain, only 7 of 15 rabbits had healed lesions at 16 to 18 weeks; among the other animals, two had chronic, progressive cavitary disease, a phenotype usually seen only with M. bovis infection. Genotypic investigation of the Erdman strain with an H37Rv-based microarray identified gene differences in the RD6 region. Southern blot and PCR structural genetic analysis showed significant differences between M. tuberculosis strains in this region. Correlation of the relative pathogenicity, including disease severity, in the rabbit model with the strain genotype may help identify stage-specific M. tuberculosis genes important in human disease.
    Type of Medium: Online Resource
    ISSN: 0019-9567 , 1098-5522
    URL: Article
    DOI: 10.1128/IAI.71.10.6004-6011.2003
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2003
    detail.hit.zdb_id: 1483247-1
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  • 2
    Online Resource
    Online Resource
    Dormancy Phenotype Displayed by Extracellular Mycobacterium tuberculosis within Artificial Granulomas in Mice
    Rockefeller University Press ; 2004
    In:  The Journal of Experimental Medicine Vol. 200, No. 5 ( 2004-09-06), p. 647-657
    Details
    In: The Journal of Experimental Medicine, Rockefeller University Press, Vol. 200, No. 5 ( 2004-09-06), p. 647-657
    Abstract: Mycobacterium tuberculosis residing within pulmonary granulomas and cavities represents an important reservoir of persistent organisms during human latent tuberculosis infection. We present a novel in vivo model of tuberculosis involving the encapsulation of bacilli in semidiffusible hollow fibers that are implanted subcutaneously into mice. Granulomatous lesions develop around these hollow fibers, and in this microenvironment, the organisms demonstrate an altered physiologic state characterized by stationary-state colony-forming unit counts and decreased metabolic activity. Moreover, these organisms show an antimicrobial susceptibility pattern similar to persistent bacilli in current models of tuberculosis chemotherapy in that they are more susceptible to the sterilizing drug, rifampin, than to the bactericidal drug isoniazid. We used this model of extracellular persistence within host granulomas to study both gene expression patterns and mutant survival patterns. Our results demonstrate induction of dosR (Rv3133c) and 20 other members of the DosR regulon believed to mediate the transition into dormancy, and that relMtb is required for Mycobacterium tuberculosis survival during extracellular persistence within host granulomas. Interestingly, the dormancy phenotype of extracellular M. tuberculosis within host granulomas appears to be immune mediated and interferon-γ dependent.
    Type of Medium: Online Resource
    ISSN: 1540-9538 , 0022-1007
    URL: Article
    DOI: 10.1084/jem.20040646
    RVK:
    XA 10000
    Language: English
    Publisher: Rockefeller University Press
    Publication Date: 2004
    detail.hit.zdb_id: 1477240-1
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  • 3
    Online Resource
    Online Resource
    Mycobacterial Genetics: The Sensibility of Antisense
    American Thoracic Society ; 2002
    In:  American Journal of Respiratory and Critical Care Medicine Vol. 165, No. 3 ( 2002-02-01), p. 318-319
    Details
    In: American Journal of Respiratory and Critical Care Medicine, American Thoracic Society, Vol. 165, No. 3 ( 2002-02-01), p. 318-319
    Type of Medium: Online Resource
    ISSN: 1073-449X , 1535-4970
    URL: Article
    DOI: 10.1164/ajrccm.165.3.2112045b
    RVK:
    XA 21200
    Language: English
    Publisher: American Thoracic Society
    Publication Date: 2002
    detail.hit.zdb_id: 1468352-0
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  • 4
    Online Resource
    Online Resource
    Potency of Wild-Type and Temperature-Sensitive Vesicular Stomatitis Virus Matrix Protein in the Inhibition of Host-Directed Gene Expression
    Elsevier BV ; 1996
    In:  Virology Vol. 225, No. 1 ( 1996-11), p. 172-180
    Details
    In: Virology, Elsevier BV, Vol. 225, No. 1 ( 1996-11), p. 172-180
    Type of Medium: Online Resource
    ISSN: 0042-6822
    URL: Article
    DOI: 10.1006/viro.1996.0585
    RVK:
    WA 15000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 1996
    detail.hit.zdb_id: 1471925-3
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Deletion of a Mycobacterium tuberculosis Proteasomal ATPase Homologue Gene Produces a Slow‐Growing Strain That Persists in Host Tissues
    Oxford University Press (OUP) ; 2006
    In:  The Journal of Infectious Diseases Vol. 194, No. 9 ( 2006-11), p. 1233-1240
    Details
    In: The Journal of Infectious Diseases, Oxford University Press (OUP), Vol. 194, No. 9 ( 2006-11), p. 1233-1240
    Type of Medium: Online Resource
    ISSN: 0022-1899 , 1537-6613
    URL: Issue
    URL: Article
    DOI: 10.1086/jid.2006.194.issue-9
    DOI: 10.1086/508288
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2006
    detail.hit.zdb_id: 1473843-0
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  • 6
    Online Resource
    Online Resource
    Loss of Pseudomonas aeruginosa PhpA Aminopeptidase Activity Results in Increased algD Transcription
    American Society for Microbiology ; 2001
    In:  Journal of Bacteriology Vol. 183, No. 15 ( 2001-08), p. 4674-4679
    Details
    In: Journal of Bacteriology, American Society for Microbiology, Vol. 183, No. 15 ( 2001-08), p. 4674-4679
    Abstract: Inactivation of Pseudomonas aeruginosa phpA , encoding a putative leucine aminopeptidase, results in increased transcription of algD . The homologous protein in Escherichia coli , PepA, is multifunctional, possessing independent aminopeptidase and DNA-binding activities. Here we provide in vitro evidence that PhpA is an aminopeptidase and show that this activity is the relevant property with regard to algD expression. This regulation occurred at the previously mapped algD transcription initiation site and was not due to activation of an alternative promoter.
    Type of Medium: Online Resource
    ISSN: 0021-9193 , 1098-5530
    URL: Article
    DOI: 10.1128/JB.183.15.4674-4679.2001
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2001
    detail.hit.zdb_id: 1481988-0
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    Identification of an Escherichia coli pepA Homolog and Its Involvement in Suppression of the algB Phenotype in Mucoid Pseudomonas aeruginosa
    American Society for Microbiology ; 1999
    In:  Journal of Bacteriology Vol. 181, No. 1 ( 1999-01), p. 107-116
    Details
    In: Journal of Bacteriology, American Society for Microbiology, Vol. 181, No. 1 ( 1999-01), p. 107-116
    Abstract: Strains of Pseudomonas aeruginosa isolated from the respiratory tracts of patients with cystic fibrosis often display a mucoid morphology due to high levels of expression of the exopolysaccharide alginate. The response regulator AlgB is required for full transcription of the alginate biosynthetic operon. Repeated attempts to demonstrate a direct interaction between AlgB and the promoter region of algD , the first gene in the alginate operon, have thus far been unsuccessful. The possibility that AlgB exerts its effect on algD indirectly exists. To identify putative genes under the control of AlgB which affect algD transcription, transposon mutagenesis of nonmucoid algB derivatives of the mucoid strain FRD1 was employed. Of approximately 3,000 transposon mutants screened, 6 were found to display phenotypes which were mucoid relative to the phenotype of the parental algB strain. The phenotypes of these mutants ranged from being only slightly mucoid to being indistinguishable from that of the original FRD1 strain. One of the particularly mucoid transposon mutants was chosen for further study. This strain was found to be disrupted in a previously uncharacterized open reading frame with 56% amino acid identity to PepA of Escherichia coli . PepA is classified as a leucine aminopeptidase, and homologs have been detected in a number of bacterial, plant, and animal species. This novel gene has been designated phpA ( P. aeruginosa homolog of pepA ). The insertional inactivation of phpA was found to correlate with the mucoid phenotype and an increase in algD transcription in the algB strain. Expression of phpA from an ectopic chromosomal locus compensated for the transposon insertion in the native phpA gene, restoring algD transcription to levels similar to those observed in the parental algB strain. While phpA expression did not appear to be under the control of AlgB at the transcriptional level, this study demonstrates that loss of phpA in an algB genetic background had a positive effect on alginate expression and, more specifically, on transcription of the alginate biosynthetic operon.
    Type of Medium: Online Resource
    ISSN: 0021-9193 , 1098-5530
    URL: Article
    DOI: 10.1128/JB.181.1.107-116.1999
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 1999
    detail.hit.zdb_id: 1481988-0
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    Isolation of Acid-Inducible Genes of Mycobacterium tuberculosis with the Use of Recombinase-Based In Vivo Expression Technology
    American Society for Microbiology ; 2003
    In:  Infection and Immunity Vol. 71, No. 3 ( 2003-03), p. 1379-1388
    Details
    In: Infection and Immunity, American Society for Microbiology, Vol. 71, No. 3 ( 2003-03), p. 1379-1388
    Abstract: A better understanding of mycobacterial gene regulation under certain stress conditions (e.g., low pH) may provide insight into mechanisms of adaptation during infection. To identify mycobacterial promoters induced at low pH, we adapted the recombinase-based in vivo expression technology (RIVET) promoter trap system for use with mycobacteria. Our results show that the TnpR recombinase of transposon γδ is active in Mycobacterium smegmatis and Mycobacterium tuberculosis . We developed a method to perform sequential double selection with mycobacteria by using RIVET, with a kanamycin preselection and a sucrose postselection. A library of M. tuberculosis DNA inserted upstream of tnpR was created, and using the double selection, we identified two promoters which are upregulated at low pH. The promoter regions drive the expression of a gene encoding a putative lipase, lipF ( Rv3487c ), as well as a PE-PGRS gene, Rv0834c , in a pH-dependent manner in both M. smegmatis and M. tuberculosis . The acid inducibility of lipF and Rv0834c was independent of the stress response sigma factor, SigF, as acid induction of the two genes in an M. tuberculosis sigF mutant strain was similar to that in the wild-type strain. No induction of lipF or Rv0834c was observed during infection of J774 murine macrophages, an observation which is in agreement with previous reports on the failure of phagosomes containing M. tuberculosis to acidify.
    Type of Medium: Online Resource
    ISSN: 0019-9567 , 1098-5522
    URL: Article
    DOI: 10.1128/IAI.71.3.1379-1388.2003
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2003
    detail.hit.zdb_id: 1483247-1
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  • 9
    Online Resource
    Online Resource
    Characterization of the Mycobacterium tuberculosis Sigma Factor SigM by Assessment of Virulence and Identification of SigM-Dependent Genes
    American Society for Microbiology ; 2007
    In:  Infection and Immunity Vol. 75, No. 1 ( 2007-01), p. 452-461
    Details
    In: Infection and Immunity, American Society for Microbiology, Vol. 75, No. 1 ( 2007-01), p. 452-461
    Abstract: Alternate sigma factors have been implicated in the survival of mycobacteria in response to specific stresses. To characterize the role of SigM in Mycobacterium tuberculosis , a sigM deletion mutant was generated by allelic exchange in the virulent CDC1551 strain. Comparing the wild-type and Δ sigM strains by complete genomic microarray, we observed a low level of baseline expression of sigM in wild-type M. tuberculosis and no significant differences in the gene expression patterns between these two strains. Alternatively, a SigM-overexpressing M. tuberculosis strain was constructed and microarray profiling revealed SigM-dependent expression of a relatively small group of genes, which included four esat-6 homologues: esxE , esxF , esxT , and esxU . An assessment of SigM-dependent promoters from the microarray analysis revealed a putative consensus sequence for M. tuberculosis SigM of −35 GGAAC and −10 CGTCR. In vitro expression studies showed that M. tuberculosis sigM transcripts accumulate slightly in stationary phase and following heat shock. To understand the role of SigM in pathogenesis, the M. tuberculosis sigM deletion strain was compared with the isogenic wild-type strain and the complemented mutant strain for survival in murine macrophages and in the mouse model. The mutant was found to have similar abilities to survive in both the resting and activated J774A.1 macrophages. Mouse organ bacterial burdens indicated that the mutant proliferated and persisted at the same level as that of the wild-type and complemented strains in lung and spleen tissues. In time-to-death experiments in the mouse model, the Δ sigM mutant exhibited lethality times comparable to those observed for the wild-type and complemented strains. These data indicate that M. tuberculosis SigM governs the expression of a small set of genes, including four esat-6 homologues, and that the loss of sigM does not confer a detectable virulence defect in the macrophages and mouse models of infection.
    Type of Medium: Online Resource
    ISSN: 0019-9567 , 1098-5522
    URL: Article
    DOI: 10.1128/IAI.01395-06
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2007
    detail.hit.zdb_id: 1483247-1
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  • 10
    Online Resource
    Online Resource
    The Rapid Development of Fluoroquinolone Resistance in M. tuberculosis
    Massachusetts Medical Society ; 2003
    In:  New England Journal of Medicine Vol. 349, No. 20 ( 2003-11-13), p. 1977-1978
    Details
    In: New England Journal of Medicine, Massachusetts Medical Society, Vol. 349, No. 20 ( 2003-11-13), p. 1977-1978
    Type of Medium: Online Resource
    ISSN: 0028-4793 , 1533-4406
    URL: Article
    DOI: 10.1056/NEJM200311133492023
    RVK:
    XA 10000
    Language: English
    Publisher: Massachusetts Medical Society
    Publication Date: 2003
    detail.hit.zdb_id: 1468837-2
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