Objective To screen out the two-component system associated with drug resistance of Mycobacterium tuberculosis by detecting the differential expression of two-component system regulator genes between multidrug resistant Mycobacterium tuberculosis strains and drug sensitive strains. Methods Total RNA of MTB was extracted from cultured MTB during the logarithmic phase in the 7H9 brook medium, and then its purity was identified. Reverse transcription was further completed. The expressing levels of TCS response regulators were quantified using SYBR Green I qRT-PCR, which aimed at finding the differential expressions between multidrug resistant strains and sensitive strains. Finally, all of differentially expressed TCS were screened out under the stress of INH, SM and LFA. Results Compared with sensitive strains,multidrug resistant strains of Rv0491, Rv3133c, Rv3143 and Rv3246c were up-regulated 1. 03, 7.11,3.48and 1.37 folds, respectively (t/t' =5. 623, -4. 196, -3. 559 and -3. 016, respectively, P ＜0. 01 ). The expressing level of other regulators had no statistical significance between muhidrug resistant strains and drug sensitive strains. Under the antibiotic pressure, the expression of Rv1027c, Rv3246c and Rv3143 showed significant changes compared with no antibiotic group. Conclusion Rv3246c and Rv3143 may be associated with MTB drug resistance and the differentially expressed genes in multi-drug resistant strains may be used as potential drug targets against drug resistant tuberculosis.%目的 检测MTB耐多药菌株和敏感菌株的TCS反应调节子的表达水平，以筛选出与MTB耐药相关的TCS。方法将7H9肉汤培养至对数生长期的MTB进行总RNA的提取和纯度鉴定；然后进行反转录，利用SYBR Green I实时荧光定量PCR方法检测MTB的TCS反应调节子表达水平，以筛查出在耐多药菌株和敏感株中差异表达的TCS反应调节子。检测1NH、SM和LFA压力下这些差异表达的TCS反应调节子的表达水平。结果 与敏感菌株相比，在耐多药菌株中Rv0491、Rv3133c、Rv3143和Rv3246c分别上调表达1.03、7.11、3.48和1.37倍，差异有统计学意义（t或t'=5.623、-4.196、-3.559、-3.016,P＜0.01）。而其余反应调节子的表达在耐多药菌株和敏感菌株之间差异均无统计学意义。在抗生素压力下，Rv1027c、Rv3246c和Rv3143的表达明显升高，Rv0491和Rv3133c则变化不明显。结论Rv3246c和Rv3143的差异表达可能是MTB耐药的重要机制之一，可为新型抗结核药物的研制提供理论依据。
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