Musser J M
Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA.
Clin Microbiol Rev. 1995 Oct;8(4):496-514. doi: 10.1128/CMR.8.4.496.
The primary theme emerging from molecular genetic work conducted with Mycobacterium tuberculosis and several other mycobacterial species is that resistance is commonly associated with simple nucleotide alterations in target chromosomal genes rather than with acquisition of new genetic elements encoding antibiotic-altering enzymes. Mutations in an 81-bp region of the gene (rpoB) encoding the beta subunit of RNA polymerase account for rifampin resistance in 96% of M. tuberculosis and many Mycobacterium leprae isolates. Streptomycin resistance in about one-half of M. tuberculosis isolates is associated with missense mutations in the rpsL gene coding for ribosomal protein S12 or nucleotide substitutions in the 16S rRNA gene (rrs). Mutations in the katG gene resulting in catalase-peroxidase amino acid alterations nad nucleotide substitutions in the presumed regulatory region of the inhA locus are repeatedly associated with isoniazid-resistant M. tuberculosis isolates. A majority of fluoroquinolone-resistant M. tuberculosis isolates have amino acid substitutions in a region of the DNA gyrase A subunit homologous to a conserved fluoroquinolone resistance-determining region. Multidrug-resistant isolates of M. tuberculosis arise as a consequence of sequential accumulation of mutations conferring resistance to single therapeutic agents. Molecular strategies show considerable promise for rapid detection of mutations associated with antimicrobial resistance. These approaches are now amenable to utilization in an appropriately equipped clinical microbiology laboratory.
对结核分枝杆菌和其他几种分枝杆菌进行分子遗传学研究得出的主要结论是，耐药性通常与靶染色体基因中的简单核苷酸改变有关，而不是与获得编码抗生素改变酶的新遗传元件有关。编码RNA聚合酶β亚基的基因（rpoB）中一个81bp区域的突变，在96%的结核分枝杆菌和许多麻风分枝杆菌分离株中导致利福平耐药。约一半的结核分枝杆菌分离株对链霉素耐药与编码核糖体蛋白S12的rpsL基因中的错义突变或16S rRNA基因（rrs）中的核苷酸替换有关。katG基因的突变导致过氧化氢酶-过氧化物酶氨基酸改变以及inhA基因座假定调控区域中的核苷酸替换，这与耐异烟肼的结核分枝杆菌分离株反复相关。大多数耐氟喹诺酮的结核分枝杆菌分离株在DNA旋转酶A亚基的一个区域中存在氨基酸替换，该区域与一个保守的氟喹诺酮耐药决定区域同源。耐多药的结核分枝杆菌分离株是由于赋予对单一治疗药物耐药性的突变的顺序积累而产生的。分子策略在快速检测与抗菌药物耐药性相关的突变方面显示出很大的前景。这些方法现在适合在配备适当的临床微生物学实验室中使用。
