Williams D L, Waguespack C, Eisenach K, Crawford J T, Portaels F, Salfinger M, Nolan C M, Abe C, Sticht-Groh V, Gillis T P
GWL Hansen's Disease Research Laboratory, Baton Rouge, LA 70894.
Antimicrob Agents Chemother. 1994 Oct;38(10):2380-6. doi: 10.1128/AAC.38.10.2380.
The emergence of rifampin-resistant strains of pathogenic mycobacteria has threatened the usefulness of this drug in treating mycobacterial diseases. Critical to the treatment of individuals infected with resistant strains is the rapid identification of these strains directly from clinical specimens. It has been shown that resistance to rifampin in Mycobacterium tuberculosis and Mycobacterium leprae apparently involves mutations in the rpoB gene encoding the beta-subunit of the RNA polymerases of these species. DNA sequences were obtained from a 305-bp fragment of the rpoB gene from 110 rifampin-resistant and 10 rifampin-susceptible strains of M. tuberculosis from diverse geographical regions throughout the world. In 102 of 110 rifampin-resistant strains 16 mutations affecting 13 amino acids were observed. No mutations were observed in rifampin-susceptible strains. No association was found between particular mutations in the rpoB gene and drug susceptibility patterns of multidrug-resistant M. tuberculosis strains. Drug-resistant M. tuberculosis strains from the same outbreak and exhibiting the same IS6110 DNA fingerprint and drug susceptibility pattern contained the same mutation in the rpoB gene. However, mutations are not correlated with IS6110 profiling outside of epidemics. The evolution of rifampin resistance as a consequence of mutations in the rpoB gene was documented in a patient who developed rifampin resistance during the course of treatment. Rifampin-resistant strains of M. leprae, Mycobacterium avium, and Mycobacterium africanum contained mutations in the rpoB gene similar to that documented for M. tuberculosis. This information served as the basis for developing a rapid DNA diagnostic assay (PCR-heteroduplex formation) for the detection of rifampin susceptibility of M. tuberculosis.
致病性分枝杆菌耐利福平菌株的出现，威胁到了该药物在治疗分枝杆菌病方面的效用。对于感染耐药菌株的个体进行治疗的关键在于，直接从临床标本中快速鉴定出这些菌株。已表明，结核分枝杆菌和麻风分枝杆菌对利福平的耐药性显然涉及编码这些菌种RNA聚合酶β亚基的rpoB基因突变。从来自世界各地不同地理区域的110株耐利福平结核分枝杆菌菌株和10株对利福平敏感的菌株中，获取了rpoB基因305bp片段的DNA序列。在110株耐利福平菌株中的102株中，观察到16个影响13个氨基酸的突变。在对利福平敏感的菌株中未观察到突变。在rpoB基因的特定突变与耐多药结核分枝杆菌菌株的药敏模式之间未发现关联。来自同一疫情且具有相同IS6110 DNA指纹和药敏模式的耐多药结核分枝杆菌菌株，在rpoB基因中含有相同的突变。然而，在疫情之外，突变与IS6110基因分型不相关。一名在治疗过程中产生利福平耐药性的患者，记录了因rpoB基因突变导致的利福平耐药性演变情况。麻风分枝杆菌、鸟分枝杆菌和非洲分枝杆菌的耐利福平菌株在rpoB基因中含有与结核分枝杆菌中记录的类似突变。这些信息为开发一种用于检测结核分枝杆菌利福平敏感性的快速DNA诊断检测方法（PCR-异源双链体形成）奠定了基础。
