本研究通过小鼠体内实验检测我国部分地区结核分枝杆菌耐药菌株的毒力，以筛选耐药结核分枝杆菌动物模型所用感染菌株。收集从我国部分省份98例结核病患者痰培养液中分离出的结核分枝杆菌，用比例法药敏试验进行结核分枝杆菌一线和二线药物的药敏试验，筛选出对二线药物敏感而对一线药物利福平或异烟肼耐药或敏感的菌株，然后进行小鼠体内毒力实验，对异烟肼耐药相关基因katG和利福平耐药相关基因rpoB测序并进行基因突变分析。从98株菌中筛选出药物敏感谱清晰的40株，在小鼠体内进行毒力实验，结果显示，共35株半数致死时间≤H37Rv的半数致死时间，其中18株耐利福平合并异烟肼、5株单耐利福平，7株单耐异烟肼、5株对利福平和异烟肼均敏感。通过小鼠毒力研究，分别筛选出基因背景清晰、半数致死时间≤7 d的耐利福平合并异烟肼的菌株1株和半数致死时间≤7 d单耐利福平和异烟肼的菌株各1株，作为小鼠耐药菌株动物模型所用感染菌株，并进一步筛选豚鼠等其他动物模型所用候选菌株。

To screen out the standard clinic strains used for animal model of drug-resistant Mycobacterium tuberculosis (M. tuberculosis), the strains were collected from tuberculosis patients in several provinces of China. The drug susceptibility test with first-line and second-line anti-tuberculosis drugs and drug-resistant gene mutant analysis were performed in 98 clinic isolations, the strains with explicit drug resistant phenotype and mutant were selected for in vivo virulence experiment in mice. Among the 40 strains with explicit drug resistant patterns, the half lethal time (LT₅₀) of 35 strains were shorter than that of H37Rv in the virulence experiment in mice. 18 in 35 strains were rifampin-resistant and isoniazid-resistant. 5 strains were rifampin-resistant, 7 strains were isoniazid-resistant, and 5 strains were sensitive to both isoniazid and rifampin. Standard strain with moderate virulence and explicite genotype was screened out for each drug resistant phenotype. For rifampin-resistance combined with isoniazid-resistance, one strain with LT₅₀≤7 d was selected as its standard strong virulence. For rifampin-resistance or isoniazid-resistance, one strain with LT₅₀≤7 d was selected as its standard strong virulence strain respectively. Each standard strain can be used as candidate standard strain used in M. tuberculosis infection model of guinea pig or other animal.