Morris S, Bai G H, Suffys P, Portillo-Gomez L, Fairchok M, Rouse D
Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland.
J Infect Dis. 1995 Apr;171(4):954-60. doi: 10.1093/infdis/171.4.954.
The molecular mechanisms of resistance to streptomycin, rifampin, and isoniazid in 53 Mycobacterium tuberculosis clinical isolates were examined. Twenty-five of 44 streptomycin-resistant strains had mutations in the rpsL gene and 5 of these had rrs gene perturbations. The region of the rpoB gene that is associated with resistance to rifampin was altered in 28 of 29 rifampin-resistant strains. Mutations in known genetic markers of isoniazid resistance were detected in 25 of 42 isoniazid-resistant isolates: 20 strains had katG gene alterations and 5 had perturbations in the inhA operon. Of the 20 multiply resistant strains with reduced sensitivity to streptomycin, rifampin, and isoniazid, 11 had mutations in genetic markers associated with resistance to each of these three drugs. These studies suggest that the primary mechanism of multiple drug resistance in tuberculosis is the accumulation of mutations in individual drug target genes.
对53株结核分枝杆菌临床分离株中对链霉素、利福平及异烟肼耐药的分子机制进行了研究。44株对链霉素耐药的菌株中，25株rpsL基因发生突变，其中5株rrs基因也有扰动。29株对利福平耐药的菌株中，28株与利福平耐药相关的rpoB基因区域发生改变。42株对异烟肼耐药的分离株中，25株检测到已知异烟肼耐药基因标记的突变：20株katG基因发生改变，5株inhA操纵子有扰动。在对链霉素、利福平及异烟肼敏感性降低的20株多重耐药菌株中，11株在与这三种药物耐药相关的基因标记上发生突变。这些研究提示，结核病多重耐药的主要机制是各个药物靶基因中突变的累积。
