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结核杆菌对D-环丝氨酸的耐药性:亲代细胞及耐药突变体中丙氨酸的突变率和转运

Resistance to D-cycloserine in the tubercle bacilli: mutation rate and transport of alanine in parental cells and drug-resistant mutants.

作者信息

David H L

出版信息

Appl Microbiol. 1971 May;21(5):888-92. doi: 10.1128/am.21.5.888-892.1971.

Abstract

A single transport system was found to accumulate l- and d-alanine, glycine and d-serine in Mycobacterium tuberculosis. The results of inhibition experiments suggested that the antibiotics d-cycloserine and O-carbamyl-d-serine were also transported by the alanine-glycine-d-serine system. A d-cycloserine-resistant permease-competent (d-CS(r)/perm(+)) mutant and a d-cycloserine-resistant permease-defective (d-CS(r)/perm(-)) mutant were isolated. The d-CS(r)/perm(-) mutant was not found to be more resistant to the drug than was the d-CS(r)/perm(+) mutant. The data were consistent with the conclusion that resistance to d-cycloserine in the tubercle bacilli is primarily due to mutations in the gene(s) controlling the enzyme d-alanyl-d-alanine synthetase. The mutation rate was calculated to be about 10(-10) mutations per bacterium per generation.

摘要

研究发现,结核分枝杆菌中存在一种单一转运系统,可积累L-丙氨酸、D-丙氨酸、甘氨酸和D-丝氨酸。抑制实验结果表明,抗生素D-环丝氨酸和O-氨甲酰-D-丝氨酸也通过丙氨酸-甘氨酸-D-丝氨酸系统进行转运。分离出了一株对D-环丝氨酸耐药且通透酶功能正常的(D-CS(r)/perm(+))突变体和一株对D-环丝氨酸耐药但通透酶缺陷的(D-CS(r)/perm(-))突变体。未发现D-CS(r)/perm(-)突变体比D-CS(r)/perm(+)突变体对该药物具有更强的耐药性。这些数据与以下结论一致:结核杆菌对D-环丝氨酸的耐药性主要是由于控制D-丙氨酰-D-丙氨酸合成酶的基因发生突变所致。计算得出突变率约为每代每个细菌10(-10)次突变。

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