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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Mutation analysis of the Mycobacterium leprae folP1 gene and dapsone resistance.
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Mutation analysis of the Mycobacterium leprae folP1 gene and dapsone resistance.

机译：麻风分枝杆菌folP1基因的突变分析和氨苯砜耐药性。

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Diaminodiphenylsulfone (dapsone) has long been used as a first-line drug worldwide for the treatment of leprosy. Diagnosis for dapsone resistance of Mycobacterium leprae by DNA tests would be of great clinical value, but the relationship between the nucleotide substitutions and susceptibility to dapsone must be clarified before use. In this study, we constructed recombinant strains of cultivable Mycobacterium smegmatis carrying the M. leprae folP1 gene with or without a point mutation, disrupting their own folP gene on the chromosome. Dapsone susceptibilities of the recombinant bacteria were measured to examine influence of the mutations. Dapsone MICs for most of the strains with mutations at codon 53 or 55 of M. leprae folP1 were 2 to 16 times as high as the MIC for the strain with the wild-type folP1 sequence, but mutations that changed Thr to Ser at codon 53 showed somewhat lower MIC values than the wild-type sequence. Strains with mutations at codon 48 or 54 showed levels of susceptibility to dapsone comparable to the susceptibility of the strain with the wild-type sequence. This study confirmed that point mutations at codon 53 or 55 of the M. leprae folP1 gene result in dapsone resistance.
机译：二氨基二苯砜（氨苯砜）长期以来一直被用作世界范围内治疗麻风病的一线药物。通过DNA检测诊断麻风分枝杆菌对氨苯砜的耐药性具有重要的临床价值，但在使用前必须弄清核苷酸取代与氨苯砜敏感性之间的关系。在这项研究中，我们构建了可携带耻垢分枝杆菌folP1基因的可培养的耻垢分枝杆菌重组菌株，带有或不带有点突变，破坏了它们在染色体上的folP基因。测量了重组细菌的氨苯砜敏感性，以检查突变的影响。对于大多数在麻风杆菌folP1的第53或55位密码子突变的菌株，其氨苯砜MICs是野生型folP1序列的菌株的MIC的2至16倍，但突变将第53位密码子的Thr变为Ser表现出比野生型序列更低的MIC值。在48或54位密码子处突变的菌株对氨苯砜的敏感性水平可与菌株对野生型序列的敏感性相媲美。这项研究证实麻风杆菌folP1基因第53或55位密码子的点突变导致氨苯砜耐药。

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