BIROn - Birkbeck Institutional Research Online

    Arylamine N-acetyltransferase is required for synthesis of mycolic acids and complex lipids in Mycobacterium bovis BCG and represents a novel drug target

    Bhakta, Sanjib and Besra, G.S. and Upton, A.M. and Parish, T. and Sholto-Douglas-Vernon, C. and Gibson, K.J. and Knutton, S. and Gordon, S. and DaSilva, R.P. and Anderton, M.C. and Sim, E. (2004) Arylamine N-acetyltransferase is required for synthesis of mycolic acids and complex lipids in Mycobacterium bovis BCG and represents a novel drug target. The Journal of Experimental Medicine 199 (9), pp. 1191-1199. ISSN 0022-1007.

    [img]
    Preview
    Text
    1191.full.pdf - Published Version of Record

    Download (339kB) | Preview

    Abstract

    Mycolic acids represent a major component of the unique cell wall of mycobacteria. Mycolic acid biosynthesis is inhibited by isoniazid, a key frontline antitubercular drug that is inactivated by mycobacterial and human arylamine N-acetyltransferase (NAT). We show that an in-frame deletion of Mycobacterium bovis BCG nat results in delayed entry into log phase, altered morphology, altered cell wall lipid composition, and increased intracellular killing by macrophages. In particular, deletion of nat perturbs biosynthesis of mycolic acids and their derivatives and increases susceptibility of M. bovis BCG to antibiotics that permeate the cell wall. Phenotypic traits are fully complemented by introduction of Mycobacterium tuberculosis nat. We infer from our findings that NAT is critical to normal mycolic acid synthesis and hence other derivative cell wall components and represents a novel target for antituberculosis therapy. In addition, this is the first report of an endogenous role for NAT in mycobacteria.

    Metadata

    Item Type: Article
    School: Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences
    Depositing User: Sarah Hall
    Date Deposited: 30 Apr 2019 11:34
    Last Modified: 02 Aug 2023 17:51
    URI: https://eprints.bbk.ac.uk/id/eprint/27364

    Statistics

    Activity Overview
    6 month trend
    184Downloads
    6 month trend
    251Hits

    Additional statistics are available via IRStats2.

    Archive Staff Only (login required)

    Edit/View Item Edit/View Item