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

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

作　　者：车洋[1] 杨天池[1] 平国华[1] 林律[1] Che Yang;Yang Tianchi;Ping Guohua;Lin Lyu(The Center of Tuberculosis Control and Prevention,Ningbo Prefectural Center for Disease Control and Prevention,Ningbo 315010,Zhejiang,China)

机构地区：[1]宁波市疾病预防控制中心结核病防制所

出　　处：《疾病监测》2019年第6期501-505,共5页Disease Surveillance

基　　金：宁波市自然科学基金(No.2018A610405);浙江省传染病疫苗与预防控制研究重点实验室开放基金~~

摘　　要：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。Objective To explore the association between efflux pump gene Rv1456 c,Rv1457 c and Rv1458 c expressions and phenotypic drug resistance of Mycobacterium tuberculosis.Methods The RNA of 102 strains of M.tuberculosis collected through drug resistance surveillance by Ningbo Prefectural Center for Disease Control and Prevention during2017-2018 were extracted.The gene expression levels of Rv1456 c,Rv1457 c and Rv1458 c were detected with real-time PCR and the data were analysed by using Mann-Whitney U test.Results The medians and interquartile ranges of expressions of Rv1457 c and Rv1458 c 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 Rv1457 c and Rv1458 c 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 overexpression rates of gene Rv1456 c and Rv1457 c between isoniazid resistant group and isoniazid sensitive group(χ^2=4.858,6.789,P<0.05).There was significant difference in over-expression rate of gene Rv1456 c between rifampicin resistant group and rifampicin sensitive group(χ^2=8.424,P<0.05).There was significant difference in over-expression rate of gene Rv1457 c between streptomycin resistant group and streptomycin sensitive group(χ^2=4.545,P<0.05).There were significant differences in over-expression rates of gene Rv1456 c and Rv1457 c between ethambutol resistant group and ethambutol sensitive group(χ^2=5.142,10.202,P<0.05).Conclusion The increases in expressions of ATP-binding cassette efflux pump gene Rv1457 c and Rv1458 c are associated with rifampicin resistance of M.tuberculosis.

关 键 词：外排泵 抗药性 结核分枝杆菌 基因表达 

分 类 号：R378.9[医药卫生—病原生物学]