Effect of rpoB mutations conferring rifampin resistance on fitness of Mycobacterium tuberculosis
Effect of rpoB mutations conferring rifampin resistance on fitness of Mycobacterium tuberculosis
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DOI：
10.1128/aac.48.4.1289-1294.2004
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发表时间：
2004-04-01
影响因子：
4.9
通讯作者：
Andersson, DI
中科院分区：
文献类型：
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作者：
Mariam, DH;Mengistu, Y;Andersson, DI
利福平是用于治疗结核感染的主要药物，并且利福平耐药性的增加代表了世界范围的临床问题。对利福平的耐药性是由rpoB基因突变引起的，rpoB基因编码RNA聚合酶的β亚基。我们研究了三种不同的rpoB突变对结核分枝杆菌适应性的影响。利福平耐药突变株是从临床分离的M.结核病（菌株Harlingen）在体外的突变频率为2.3 × 10（-8）。在rpoB基因的突变进行了鉴定，并通过与敏感的亲本菌株在实验室培养基中的竞争，并通过在巨噬细胞系和实验室培养基中的单一培养物的三个定义的突变体的生长速率进行了测量。所有突变体在三个测定中均显示生长速率降低。根据特定的突变体和测定系统，突变体的相对适合度在0.29和0.96之间变化（敏感菌株的相对适合度设定为1.0）。出乎意料的是，突变体的相对适合度排名在不同测定之间不同。总之，利福平耐药与成本是有条件的。
Rifampin is a major drug used in the treatment of tuberculosis infections, and increasing rifampin resistance represents a worldwide clinical problem. Resistance to rifampin is caused by mutations in the rpoB gene, encoding the beta-subunit of RNA polymerase. We examined the effect of three different rpoB mutations on the fitness of Mycobacterium tuberculosis. Rifampin-resistant mutants were isolated from a virulent clinical isolate of M. tuberculosis (strain Harlingen) in vitro at a mutation frequency of 2.3 X 10(-8). Mutations in the rpoB gene were identified, and the growth rates of three defined mutants were measured by competition with the susceptible parent strain in laboratory medium and by single cultures in a macrophage cell line and in laboratory medium. All of the mutants showed a decreased growth rate in the three assays. The relative fitness of the mutants varied between 0.29 and 0.96 (that of the susceptible strain was set to 1.0) depending on the specific mutant and assay system. Unexpectedly, the relative fitness ranking of the mutants differed between the different assays. In conclusion, rifampin resistance is associated with a cost that is conditional.