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  • 1
    Electronic Resource
    Electronic Resource
    Increased Expression of Mycobacterium tuberculosis 19 kDa Lipoprotein Obliterates the Protective Efficacy of BCG by Polarizing Host Immune Responses to the Th2 Subtype (2005)
    Oxford, UK; Malden, USA : Blackwell Science Ltd
    Scandinavian journal of immunology 61 (2005), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Mycobacterium tuberculosis can not only neutralize immune effector functions, but also has the ability to modulate host-signalling cascades involved in the development of these responses. The 19 kDa antigen (Rv3763), a lipoprotein of M. tuberculosis, elicits high levels of interleukin (IL)-12 from macrophages in addition to its powerful immunomodulatory properties, leading to suppression of antigen-presentation signalling cascades. The present study was aimed at analysing the effect of overexpression of this antigen on the immunostimulatory properties of M. bovis Bacille Calmette–Guérin (BCG). We have constructed a recombinant BCG strain (rBCG19N) producing higher levels of the 19 kDa antigen in both the cytoplasmic (approximately eightfold) and extracellular (approximately fivefold) fractions as compared to the wildtype BCG. Immunization of mice with rBCG19N elicited high levels of interferon-gamma (IFN-γ) and relatively low levels of IL-10 against the purified 19 kDa antigen. However, in response to total BCG sonicate, mice immunized with rBCG19N produced significantly high levels of IL-10 with relatively very low levels of IFN-γ. This polarization of the host immune responses towards T-helper 2 subtype resulted in complete abrogation of the protective efficacy of BCG, when rBCG19N was used as a live vaccine against M. tuberculosis challenge in guinea pigs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.2005.01569.x
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  • 2
    Electronic Resource
    Electronic Resource
    Disruption of mptpB impairs the ability of Mycobacterium tuberculosis to survive in guinea pigs (2003)
    Oxford, UK : Blackwell Science Ltd
    Molecular microbiology 50 (2003), S. 0 
    Details
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Protein tyrosine kinases and tyrosine phosphatases from several bacterial pathogens have been shown to act as virulence factors by modulating the phosphorylation and dephosphorylation of host proteins. The identification and characterization of two tyrosine phosphatases namely MptpA and MptpB from Mycobacterium tuberculosis has been reported earlier. MptpB is secreted by M. tuberculosis into extracellular mileu and exhibits a pH optimum of 5.6, similar to the pH of the lysosomal compartment of the cell. To determine the role of MptpB in the pathogenesis of M. tuberculosis, we constructed a mptpB mutant strain by homologous recombination and compared the ability of parent and the mutant strain to survive intracellularly. We show that disruption of the mptpB gene impairs the ability of the mutant strain to survive in activated macrophages and guinea pigs but not in resting macrophages suggesting the importance of its role in the host–pathogen interaction. Infection of guinea pigs with the mutant strain resulted in a 70-fold reduction in the bacillary load of spleens in infected animals as compared with the bacillary load in animals infected with the parental strain. Upon reintroduction of the mptpB gene into the mutant strain, the complemented strain was able to establish infection and survive in guinea pigs at rates comparable to the parental strain. These observations demonstrate a   role   of MptpB in the pathogenesis   of M. tuberculosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2958.2003.03712.x
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  • 3
    Electronic Resource
    Electronic Resource
    Human tuberculosis sera show prominent antibody responses to particulate fractions ofMycobacterium tuberculosis (1991)
    Springer
    Journal of clinical immunology 11 (1991), S. 74-77 
    Details
    ISSN: 1573-2592
    Keywords: Tuberculosis ; serology ; Western blot ; diagnosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Sera from smear-positive pulmonary tuberculosis patients and normal control subjects in Madras were analyzed by Western blotting for their reactivity with soluble and particulate (membrane-rich and cell wall-rich) antigen fractions extracted by sonication fromMycobacterium tuberculosis H37Rv. Discrimination between patient and control sera was best with particulate antigen fractions: 60% of patient sera reacted with a 38-kD antigen band and 90% reacted with a 55-kD band. Reactions of control sera with the 38- and 55-kD bands were infrequent and faint. The results suggest that a serodiagnostic test might be based on quantitation of responses to these two antigens.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00917743
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    Paper (German National Licenses)
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