Mikusová K, Slayden R A, Besra G S, Brennan P J
Department of Microbiology, Colorado State University, Fort Collins 80523-1677, USA.
Antimicrob Agents Chemother. 1995 Nov;39(11):2484-9. doi: 10.1128/AAC.39.11.2484.
The effect of ethambutol (EMB) is primarily on polymerization steps in the biosynthesis of the arabinan component of cell wall arabinogalactan (AG) of Mycobacterium smegmatis. Inhibition of the synthesis of the arabinan of lipoarabinomannan (LAM) occurred later, and thus in the cases of AG and LAM, the polymerization of D-arabinofuranose apparently involves separate pathways. While the synthesis of these arabinans was normal in an EMB-resistant isogeneic strain, the addition of EMB to the resistant strain resulted in partial inhibition of the synthesis of the arabinan of LAM and the emergence of a novel, truncated form of LAM, indicating partial susceptibility of the resistant gene(s) and providing a new intermediate in the LAM biosynthetic sequence. A consequence of inhibition of AG arabinan biosynthesis is the lack of new sites for mycolate attachment and thus the channeling of mycolate residues into a variety of free lipids which then accumulate. The primary biochemical effects of EMB can be explained by postulating separate AG and LAM pathways catalyzed by a variety of extramembranous arabinosyl transferases with various degrees of sensitivity to EMB.
乙胺丁醇（EMB）的作用主要针对耻垢分枝杆菌细胞壁阿拉伯半乳聚糖（AG）的阿拉伯聚糖成分生物合成中的聚合步骤。脂阿拉伯甘露聚糖（LAM）阿拉伯聚糖的合成抑制出现较晚，因此在AG和LAM的情况中，D - 阿拉伯呋喃糖的聚合显然涉及不同途径。虽然这些阿拉伯聚糖的合成在耐EMB的同基因菌株中是正常的，但向该耐药菌株中添加EMB会导致LAM阿拉伯聚糖合成的部分抑制以及一种新型截短形式LAM的出现，这表明耐药基因存在部分敏感性，并在LAM生物合成序列中提供了一个新的中间体。AG阿拉伯聚糖生物合成受抑制的一个后果是缺乏新的霉菌酸附着位点，从而导致霉菌酸残基进入多种游离脂质并积累。EMB的主要生化作用可以通过假定由多种对EMB敏感度不同的膜外阿拉伯糖基转移酶催化的不同AG和LAM途径来解释。
