Arylamine N-acetyltransferase is required for synthesis of mycolic acids and complex lipids in Mycobacterium bovis BCG and represents a novel drug target.
Arylamine N-acetyltransferase is required for synthesis of mycolic acids and complex lipids in Mycobacterium bovis BCG and represents a novel drug target.
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芳基胺N-乙酰转移酶是牛肉杆菌BCG中合成霉菌酸和复杂脂质所必需的，它代表了一种新型的药物靶标。
DOI：
10.1084/jem.20031956
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发表时间：
2004-05-03
影响因子：
15.3
通讯作者：
Sim, E
中科院分区：
文献类型：
--
作者：
Bhakta, S;Besra, GS;Upton, AM;Parish, T;Sholto-Douglas-Vernon, C;Gibson, KJC;Knutton, S;Gordon, S;daSilva, RP;Anderton, MC;Sim, E
分枝菌酸是分枝杆菌独特细胞壁的主要成分。分枝菌酸的生物合成受到异烟肼的抑制，异烟肼是一种关键的一线抗结核药物，可被分枝杆菌和人芳胺N-乙酰转移酶（NAT）灭活。我们表明，在框内删除牛分枝杆菌BCG nat的结果延迟进入对数期，改变形态，改变细胞壁脂质组成，并增加巨噬细胞的细胞内杀伤。特别是，nat的缺失干扰分枝菌酸及其衍生物的生物合成，并增加M.牛的卡介苗转化为渗透细胞壁的抗生素。表型性状是完全补充结核分枝杆菌自然引入。我们推断，从我们的研究结果，NAT是至关重要的正常分枝菌酸的合成，因此其他衍生细胞壁成分，并代表了一个新的抗结核治疗的目标。此外，这是第一份关于NAT在分枝杆菌中的内源性作用的报告。
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.
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影响因子：
120.7
作者：
Dye, C;Scheele, S;Raviglione, RC
通讯作者：
Raviglione, RC
影响因子：
2.8
作者：
Indrigo, J;Hunter, RL;Actor, JK
通讯作者：
Actor, JK
影响因子：
56.9
作者：
Moody, DB;Reinhold, BB;Porcelli, SA
通讯作者：
Porcelli, SA
影响因子：
4.8
作者：
Mushtaq, A;Payton, M;Sim, E
通讯作者：
Sim, E
DOI：
10.1111/j.1574-695x.1996.tb00087.x
发表时间：
1996-10-01
影响因子：
--
作者：
Klegerman, ME;Devadoss, PO;Groves, MJ
通讯作者：
Groves, MJ