Gillis T P, Williams D L
Molecular Biology Department, Laboratory Research Branch, National Hansen's Disease Programs, Louisiana State University, Baton Rouge, Louisiana, USA.
Lepr Rev. 2000 Dec;71 Suppl:S91-5.
The folP1 gene of Mycobacterium leprae, which encodes dihydropteroate synthase (DHPS), was studied for the presence of mutations associated with resistance to dapsone (DDS). When the folP1 of several DDS-resistant clinical isolates of M. leprae were sequenced, two missense mutations were identified. One mutation occurred at codon 53, substituting isoleucine for threonine in DHPS-1, and a second mutation occurred in codon 55, substituting arginine for proline. DNA sequencing of strains of M. leprae resistant to 0.01 g% DDS in the mouse diet revealed that 13 of 14 strains contained either the 53 or 55 folP1 mutation. None of the susceptible strains and only one of five strains resistant to 0.001 g% DDS revealed a mutation in folP1, suggesting that only high-level DDS resistance is associated with the mutations identified in folP1. Development and application of simple molecular tests to assess drug-related mutations in M. leprae could establish current levels of drug resistance in leprosy as a reference point for future monitoring of drug resistance at the global level.
对麻风分枝杆菌中编码二氢蝶酸合酶（DHPS）的folP1基因进行了研究，以确定是否存在与氨苯砜（DDS）耐药性相关的突变。对几株氨苯砜耐药的麻风分枝杆菌临床分离株的folP1进行测序时，发现了两个错义突变。一个突变发生在第53位密码子，在DHPS-1中苏氨酸被异亮氨酸取代，另一个突变发生在第55位密码子，脯氨酸被精氨酸取代。对小鼠饲料中0.01 g%氨苯砜耐药的麻风分枝杆菌菌株进行DNA测序发现，14株菌株中有13株含有folP1第53位或第55位突变。敏感菌株均未发现folP1突变，对0.001 g%氨苯砜耐药的5株菌株中只有1株发现folP1突变，这表明只有高水平的氨苯砜耐药性与folP1中鉴定出的突变有关。开发和应用简单的分子检测方法来评估麻风分枝杆菌中与药物相关的突变，可以确定当前麻风病的耐药水平，作为未来全球耐药性监测的参考点。
