{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T04:04:49Z","timestamp":1768968289475,"version":"3.49.0"},"reference-count":48,"publisher":"Rockefeller University Press","issue":"9","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,5,3]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1084\/jem.20031956","type":"journal-article","created":{"date-parts":[[2004,4,27]],"date-time":"2004-04-27T00:53:52Z","timestamp":1083027232000},"page":"1191-1199","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":89,"title":["Arylamine <i>N<\/i>-Acetyltransferase Is Required for Synthesis of Mycolic Acids and Complex Lipids in <i>Mycobacterium bovis<\/i> BCG and Represents a Novel Drug Target"],"prefix":"10.1084","volume":"199","author":[{"given":"Sanjib","family":"Bhakta","sequence":"first","affiliation":[{"name":"1Department of Pharmacology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gurdyal S.","family":"Besra","sequence":"additional","affiliation":[{"name":"3Department of Biosciences and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna M.","family":"Upton","sequence":"additional","affiliation":[{"name":"1Department of Pharmacology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanya","family":"Parish","sequence":"additional","affiliation":[{"name":"5Department of Medical Microbiology, Barts and the London, Queen Mary's School of Medicine and Dentistry, London E1 2AD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolyn","family":"Sholto-Douglas-Vernon","sequence":"additional","affiliation":[{"name":"1Department of Pharmacology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin J.C.","family":"Gibson","sequence":"additional","affiliation":[{"name":"3Department of Biosciences and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart","family":"Knutton","sequence":"additional","affiliation":[{"name":"4Institute of Child Health, University of Birmingham, Birmingham B4 6NH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siamon","family":"Gordon","sequence":"additional","affiliation":[{"name":"2Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosangela P.","family":"daSilva","sequence":"additional","affiliation":[{"name":"2Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew C.","family":"Anderton","sequence":"additional","affiliation":[{"name":"1Department of Pharmacology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edith","family":"Sim","sequence":"additional","affiliation":[{"name":"1Department of Pharmacology and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[2004,4,26]]},"reference":[{"key":"2023072512301463800_BIB1","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1001\/jama.282.7.677","volume":"282","year":"1999","journal-title":"JAMA."},{"key":"2023072512301463800_BIB2","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1126\/science.257.5073.1055","volume":"257","year":"1992","journal-title":"Science."},{"key":"2023072512301463800_BIB3","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1164\/ajrccm.149.5.8173779","volume":"149","year":"1994","journal-title":"Am. 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