Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.7.1.2 (nitrate reductase)
 3,861 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mycobacterium tuberculosis and Mycobacterium bovis cause tuberculosis, which is responsible for the deaths of more people each year than any other bacterial infectious disease. Disseminated disease with Mycobacterium bovis BCG, the only currently available vaccine against tuberculosis, occurs in immunocompetent and immunodeficient individuals. Although mycobacteria are obligate aerobes, they are thought to face an anaerobic environment during infection, notably inside abscesses and granulomas. The purpose of this study was to define a metabolic pathway that could allow mycobacteria to exist under these conditions. Recently, the complete genome of M. tuberculosis has been sequenced, and genes homologous to an anaerobic nitrate reductase (narGHJI), an enzyme allowing nitrate respiration when oxygen is absent, were found. Here, we show that the narGHJI cluster of M. tuberculosis is functional as it conferred anaerobic nitrate reductase activity to Mycobacterium smegmatis. A narG mutant of M. bovis BCG was generated by targeted gene deletion. The mutant lacked the ability to reduce nitrate under anaerobic conditions. Both mutant and M. bovis BCG wild type grew equally well under aerobic conditions in vitro. Histology of immunodeficient mice (SCID) infected with M. bovis BCG wild type revealed large granulomas teeming with acid-fast bacilli; all mice showed signs of clinical disease after 50 days and succumbed after 80 days. In contrast, mice infected with the mutant had smaller granulomas containing fewer bacteria; these mice showed no signs of clinical disease after more than 200 days. Thus, it seems that nitrate respiration contributes significantly to virulence of M. bovis BCG in immunodeficient SCID mice.
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PMID:Anaerobic nitrate reductase (narGHJI) activity of Mycobacterium bovis BCG in vitro and its contribution to virulence in immunodeficient mice. 1071 84

We report Mycobacterium bovis BCG infection in two children vaccinated with BCG (Tokyo strain) on the first day of life. Their diagnoses were made by biopsy of skin lesions and pus from an anterior chest wall abscess, respectively, yielding a positive culture of mycobacteria fully susceptible to rifampicin, isoniazid and ethambutol, but resistant to pyrazinamide. M. bovis BCG was identified by a negative niacin test, absence of nitrate reductase and resistance to pyrazinamide and cycloserine. The diagnoses were further confirmed by a combination of an allele-specific polymerase chain reaction ated strain of Mycobacterium bovis, is the only available vaccine for the prevention of tuberculosis. Although complications are rare after BCG vaccination and the outcome is usually favourable, serious BCG infections can occur. We report two cases of M. bovis BCG infection in children, a 4-year-old immunocompetent girl and an 8-month-old immunodeficient boy. To our knowledge, this is the first report of BCG complications in children in which two recently developed polymerase chain reaction (PCR) based methods were used for rapid identification of M. bovis BCG infection. (PCR) and a multiplex PCR method. Based on the drug susceptibility results, treatment with rifampicin, isoniazid and ethambutol was instituted. One patient (Case 1) improved clinically and is well after treatment. However, the other patient with severe combined immunodeficiency died of disseminated BCG infection in spite of intensive anti-tuberculosis therapy. Although BCG is considered to be a safe vaccine, it should be kept in mind that complications related to BCG do occur.
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PMID:Utility of PCR assays for rapid diagnosis of BCG infection in children. 1133 59

Mycobacterium bovis BCG, the only presently available vaccine against tuberculosis, was obtained from virulent M. bovis after serial passages in vitro. The vaccine strain retained at least some of its original virulence, as it persists in immune-competent hosts and occasionally may cause fatal disease in immune-deficient hosts. Mycobacterial persistence in vivo is thought to depend on anaerobic metabolism, an apparent paradox since all mycobacteria are obligate aerobes. Here we report that M. bovis BCG lacking anaerobic nitrate reductase (NarGHJI), an enzyme essential for nitrate respiration, failed to persist in the lungs, liver, and kidneys of immune-competent (BALB/c) mice. In immune-deficient (SCID) mice, however, bacilli caused chronic infection despite disruption of narG, even if growth of the mutant was severely impaired in lungs, liver, and kidneys. Persistence and growth of BCG in the spleens of either mouse strain appeared largely unaffected by lack of anaerobic nitrate reductase, indicating that the role of the enzyme in pathogenesis is tissue specific. These data suggest first that anaerobic nitrate reduction is essential for metabolism of M. bovis BCG in immune-competent but not immune-deficient mice and second that its role in mycobacterial disease is tissue specific, both of which are observations with important implications for pathogenesis of mycobacteria and vaccine development.
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PMID:Dependence of Mycobacterium bovis BCG on anaerobic nitrate reductase for persistence is tissue specific. 1174 94