Tomiyasu I, Yano I
Arch Microbiol. 1984 Apr;137(4):316-23. doi: 10.1007/BF00410728.
The mycolic acid compositions of Nocardia rubra and related bacteria grown in media containing different concentrations of antituberculous isonicotinic acid hydrazide (INH) were determined in detail by gas chromatography-mass spectrometry. On the basis of molecular species composition, average carbon numbers of mycolic acids were calculated. In Nocardia rubra, N. lutea and Rhodococcus rhodochrous IFO-13161, the ratio of mycolic to non-mycolic fatty acids and the average carbon numbers of mycolic acids were decreased at the INH concentrations of higher than 1 microgram/ml, paralleling with the significant inhibition of growth. In above three species the synthesis of longer chain mycolic acids (longer than C44 or C46 ) was inhibited more significantly than shorter homologues such as C38 or C40 . In contrast, neither growth inhibition nor change in corynomycolic acid composition was observed in Corynebacteria xerosis and Rhodococcus rhodochrous IFO-13165 at the concentration region of INH up to 100 micrograms/ml. The direct mass fragmentographic analysis of the trimethylsilylated (TMS) derivatives of mycolic acid methyl esters, monitoring [M-15] ions of individual molecular species, revealed that the chain shortening of total mycolic acid molecule by INH occurred more greatly in more highly unsaturated subclasses than in less unsaturated subclasses. Furthermore, mass fragmentographic analysis, monitoring fragment ions (A) and (B), due to straight chain and branched chain alkyl units, respectively, demonstrated the inhibition of mycolic acids was not attributed to the shortening of alpha-alkyl chain, but to the inhibition of chain elongation of C28 to C32 straight chain meromycolic acids. It was also indicated the amounts of trehalose mono- and di- mycolate (cord factor) decreased significantly with the addition of INH (1 to 20 micrograms/ml) in the above strains. From the results obtained above, INH appeared to inhibit the synthesis of mycolic acids longer than C44 or C46 specifically by inhibiting chain elongation or desaturation of precursor long chain fatty acids longer than C28 or C30.
采用气相色谱 - 质谱联用技术，详细测定了在含有不同浓度抗结核异烟肼（INH）的培养基中生长的红色诺卡氏菌及相关细菌的分枝菌酸组成。根据分子种类组成，计算了分枝菌酸的平均碳原子数。在红色诺卡氏菌、藤黄诺卡氏菌和红球菌IFO - 13161中，当INH浓度高于1微克/毫升时，分枝菌酸与非分枝菌酸脂肪酸的比例以及分枝菌酸的平均碳原子数均降低，这与生长受到显著抑制平行。在上述三种菌中，长链分枝菌酸（长于C44或C46）的合成比短链同系物如C38或C40受到更显著的抑制。相比之下，在干燥棒状杆菌和红球菌IFO - 13165中，在高达100微克/毫升的INH浓度范围内，未观察到生长抑制或棒状分枝菌酸组成的变化。对分枝菌酸甲酯的三甲基硅烷基化（TMS）衍生物进行直接质量碎片分析，监测各个分子种类的[M - 15]离子，结果表明，INH使总分枝菌酸分子的链缩短在高度不饱和亚类中比在低度不饱和亚类中更显著。此外，质量碎片分析监测分别由于直链和支链烷基单元产生的碎片离子（A）和（B），结果表明分枝菌酸的抑制并非归因于α - 烷基链的缩短，而是归因于C28至C32直链分枝菌酸链延长的抑制。还表明在上述菌株中添加INH（1至20微克/毫升）后，海藻糖单分枝菌酸酯和二分枝菌酸酯（索状因子）的量显著减少。根据上述结果，INH似乎通过抑制长于C28或C30的前体长链脂肪酸的链延长或去饱和作用，特异性地抑制长于C44或C46的分枝菌酸的合成。
