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    'Happy the man, who, studying nature's laws, Thro' known effects can trace the secret cause.' Do we have enough pieces to solve the pyrazinamide puzzle?

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    Authors
    Anthony, R M
    den Hertog, A L
    van Soolingen, D
    Type
    Article
    Language
    en
    
    Metadata
    Show full item record
    Title
    'Happy the man, who, studying nature's laws, Thro' known effects can trace the secret cause.' Do we have enough pieces to solve the pyrazinamide puzzle?
    Published in
    Tijdschrift J Antimicrob Chemother 2018; advance online publication (ahead of print)
    Publiekssamenvatting
    A low pH was assumed to be required for the activity of pyrazinoic acid (the active form of pyrazinamide) against Mycobacterium tuberculosis, but recently activity has been demonstrated at neutral pH. Renewed interest in pyrazinamide has led to an increasing number of potential targets and the suspicion that pyrazinamide is a 'dirty drug'. However, it is our opinion that the recent demonstration that pyrazinoic acid is active against PanD provides an alternative explanation for the secret of pyrazinamide's unusual activity. In this article we propose that PanD is the primary target of pyrazinoic acid but expression of pyrazinoic acid susceptibility requires an intact stress response. As the mycobacterial stress response requires the interaction of a number of genes, disruption of any could result in an inability to enter the susceptible phenotype. We believe this model can explain most of the recent observations of the seemingly diverse spectrum of activity of pyrazinamide.
    DOI
    10.1093/jac/dky060
    PMID
    29528413
    URI
    http://hdl.handle.net/10029/621682
    ae974a485f413a2113503eed53cd6c53
    10.1093/jac/dky060
    Scopus Count
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