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结核分枝杆菌inhA操纵子中的mabA基因编码一种3-酮酰基还原酶,该酶不能赋予对异烟肼的抗性。

The mabA gene from the inhA operon of Mycobacterium tuberculosis encodes a 3-ketoacyl reductase that fails to confer isoniazid resistance.

作者信息

Banerjee Asesh, Sugantino Michele, Sacchettini James C, Jacobs William R

机构信息

Department of Microbiology and Immunologyl, Howard Hughes Medical Institute, and Department of Biochemistry.

Albert Einstein College of MedicineBronx, NY 10461USA.

出版信息

Microbiology (Reading). 1998 Oct;144 ( Pt 10):2697-2704. doi: 10.1099/00221287-144-10-2697.

Abstract

A target of the anti-tuberculosis drugs isoniazid (INH) and ethionamide (ETH) has been shown to be an enoyl reductase, encoded by the inhA gene. The mabA (mycolic acid biosynthesis A) gene is located immediately upstream of inhA in Mycobacterium tuberculosis, Mycobacterium bovis and Mycobacterium smegmatis. The MabA protein from M. tuberculosis was expressed in Escherichia coli and shown to have 3-ketoacyl reductase activity, consistent with a role in mycolic acid biosynthesis. In M. smegmatis, inhA and mabA are independently transcribed, but in M. tuberculosis and M. bovis BCG, mabA and inhA constitute a single operon. Several INH-ETH-resistant M. tuberculosis clinical isolates contain point mutations in the ribosome-binding site of mabA in the mabA-inhA operon. However, genetic dissection of this operon reveals that the INH-ETH-resistance phenotype is encoded only by inhA, and not by mabA.

摘要

抗结核药物异烟肼(INH)和乙硫异烟胺(ETH)的一个靶点已被证明是一种烯酰还原酶,由inhA基因编码。mabA(分枝菌酸生物合成A)基因位于结核分枝杆菌、牛分枝杆菌和耻垢分枝杆菌中inhA的紧邻上游。来自结核分枝杆菌的MabA蛋白在大肠杆菌中表达,并显示具有3-酮酰还原酶活性,这与它在分枝菌酸生物合成中的作用一致。在耻垢分枝杆菌中,inhA和mabA是独立转录的,但在结核分枝杆菌和卡介苗中,mabA和inhA构成一个单一的操纵子。几种耐INH-ETH的结核分枝杆菌临床分离株在mabA-inhA操纵子的mabA核糖体结合位点含有点突变。然而,对该操纵子的基因剖析表明,耐INH-ETH的表型仅由inhA编码,而不由mabA编码。

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