外排泵基因Rv1456c、Rv1457c、Rv1458c表达与结核分枝杆菌耐药关系探讨

目的研究外排泵基因Rv1456c、Rv1457c、Rv1458c的表达与结核分枝杆菌(MTB)不同耐药表型的关系。方法提取2017-2018年浙江省宁波市疾病预防控制中心耐药监测期间收集的102株MTB核糖核酸(RNA),应用实时荧光定量PCR方法检测ABC转运蛋白超家族外排泵基因Rv1456c、Rv1457c、Rv1458c的表达量,采用Mann-Whitney U检验分析外排泵基因表达在不同耐药表型菌株中的差异。结果 Rv1457c和Rv1458c基因表达量在利福平耐药组中的中位数及四分位数间距[0.507(0.378~1.444),1.842(1.325~2.628)]高于利福平敏感组[0.418(0.357~0.618),1.545 (1.189~2.065)],差异有统计学意义(Z=2.030、2.108,均P<0.05)。耐多药组Rv1457c和Rv1458c基因表达量的中位数及四分位数间距[0.538(0.419~1.490),1.941(1.471~2.659)],高于非耐多药组[0.415 (0.337~0.618),1.533 (1.122~2.056)],差异有统计学意义(Z=2.865、2.896,均P<0.05)。异烟肼耐药组和敏感组中Rv1456c、Rv1457c的高表达率均存在差异(χ^2=4.858、6.789,均P<0.05),利福平耐药组和敏感组中Rv1456c的高表达率差异有统计学意义(χ^2=8.424,P<0.05),链霉素耐药组和敏感组中Rv1457c的高表达率差异有统计学意义(χ^2=4.545,P<0.05),乙胺丁醇耐药组和敏感组中Rv1456c、Rv1457c的高表达率差异均有统计学意义(χ^2=5.142、10.202,均P<0.05)。结论外排泵基因Rv1457c、Rv1458c的相对表达量增加与MTB对利福平耐药有关。

Drug efflux pump Rv1456c, Rv1457c and Rv1458c gene expressions with drug resistance of Mycobacterium tuberculosis

ObjectiveTo explore the association between efflux pump gene Rv1456c, Rv1457c and Rv1458c expressions and phenotypic drug resistance of Mycobacterium tuberculosis.MethodsThe RNA of 102 strains of M. tuberculosis collected through drug resistance surveillance by Ningbo Prefectural Center for Disease Control and Prevention during 2017—2018 were extracted. The gene expression levels of Rv1456c, Rv1457c and Rv1458c were detected with real-time PCR and the data were analysed by using Mann-Whitney U test.ResultsThe medians and interquartile ranges of expressions of Rv1457c and Rv1458c in rifampicin resistant group ［0.507 (0.378–1.444), 1.842 (1.325–2.628)］, were higher than those in rifampicin sensitive group ［0.418 (0.357–0.618), 1.545 (1.189–2.065)］, the differences were significant (Z＝2.030,2.108, P＜0.05). The medians and interquartile ranges of expressions of Rv1457c and Rv1458c in multidrug resistant group ［0.538 (0.419–1.490), 1.941 (1.471–2.659)］ were higher than those in non-multidrug resistant group ［0.415 (0.337–0.618), 1.533 (1.122–2.056)］, the differences were significant (Z＝2.865,2.896, P＜0.05). There were significant difference in over-expression rates of gene Rv1456c and Rv1457c between isoniazid resistant group and isoniazid sensitive group (χ2＝4.858,6.789, P＜0.05). There was significant difference in over-expression rate of gene Rv1456c between rifampicin resistant group and rifampicin sensitive group (χ2＝8.424, P＜0.05). There was significant difference in over-expression rate of gene Rv1457c between streptomycin resistant group and streptomycin sensitive group (χ2＝4.545, P＜0.05). There were significant differences in over-expression rates of gene Rv1456c and Rv1457c between ethambutol resistant group and ethambutol sensitive group (χ2＝5.142, 10.202,P＜0.05). ConclusionThe increases in expressions of ATP-binding cassette efflux pump gene Rv1457c and Rv1458c are associated with rifampicin resistance of M. tuberculosis.