本文選題：分枝桿菌　切入點：結核　出處：《中國抗生素雜志》2017年02期 　論文類型：期刊論文

【摘要】：目的體外誘導并獲得結核分枝桿菌(MTB)對PA-824的耐藥菌株。方法選取MTB標準株H_(37)Rv,在PA-824濃度二倍遞增的含藥培養(yǎng)基上進行傳代培養(yǎng),逐步誘導菌株對PA-824耐藥,測定多種抗結核藥物對PA-824耐藥株的最低抑菌濃度(minimal inhibitory concentration,MIC),并對耐藥株測序鑒定ddn和fgd1基因的突變情況。將耐藥株在無藥固體培養(yǎng)基上連續(xù)傳代培養(yǎng)10代以觀察耐藥穩(wěn)定性。結果 H_(37)Rv經逐步誘導后得到5株MTB單克隆,它們對PA-824的MIC值是誘導前8倍以上,且對TBA-354同時發(fā)生交叉耐藥。測序結果顯示fgd1基因未發(fā)生突變,但5株均檢測到ddn基因突變。耐藥株在無藥固體培養(yǎng)基上連續(xù)傳代10代后,MIC值無明顯變化。結論通過二倍遞增體外誘導可以獲得對2種硝基咪唑類(nitroimidazoles)藥物均耐藥的MTB菌株;MTB對硝基咪唑類藥物的耐藥可能與ddn基因突變有關;MTB對硝基咪唑類藥物的耐藥穩(wěn)定性較強,不易復敏。
[Abstract]:Objective to induce and obtain the drug resistant strains of Mycobacterium tuberculosis to PA-824 in vitro. Methods the standard MTB strain Hast37 Rv.Methods the strains were subcultured on the drug containing medium with double increasing PA-824 concentration, and the drug resistance to PA-824 was induced step by step. The minimal inhibitory concentration of antimicrobial agents against PA-824 resistant strains was determined, and the mutations of ddn and fgd1 genes were identified by sequencing the resistant strains. The resistant strains were cultured on drug-free solid medium for 10 generations to observe drug resistance. Results after induction, 5 MTB monoclonal strains were obtained. Their MIC value to PA-824 was more than 8 times higher than that before induction, and they also had cross resistance to TBA-354. Sequencing showed that the fgd1 gene was not mutated. However, ddn gene mutations were detected in all of the 5 strains. There was no significant change in the ddn values of drug-resistant strains after continuous passage on drug-free solid medium for 10 generations. Conclusion two nitroimidazoles-based nitroimidazoles-resistant drugs can be obtained by twice increasing induction in vitro. The resistance of MTB to nitroimidazoles may be related to the mutation of ddn gene. It is not easy to re-sensitize.
【作者單位】： 首都醫(yī)科大學附屬北京胸科醫(yī)院北京市結核病胸部腫瘤研究所;
【基金】：國家科技新藥創(chuàng)制重大專項子課題(No.2015ZX09102007-015) 北京市醫(yī)院管理局臨床醫(yī)學發(fā)展專項經費資助(No.ZYLX201304)
【分類號】：R446.5

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