本文選題：分枝桿菌　切入點(diǎn)：結(jié)核　出處：《中國(guó)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(dǎo)并獲得結(jié)核分枝桿菌(MTB)對(duì)PA-824的耐藥菌株。方法選取MTB標(biāo)準(zhǔn)株H_(37)Rv,在PA-824濃度二倍遞增的含藥培養(yǎng)基上進(jìn)行傳代培養(yǎng),逐步誘導(dǎo)菌株對(duì)PA-824耐藥,測(cè)定多種抗結(jié)核藥物對(duì)PA-824耐藥株的最低抑菌濃度(minimal inhibitory concentration,MIC),并對(duì)耐藥株測(cè)序鑒定ddn和fgd1基因的突變情況。將耐藥株在無(wú)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(jié)果 H_(37)Rv經(jīng)逐步誘導(dǎo)后得到5株MTB單克隆,它們對(duì)PA-824的MIC值是誘導(dǎo)前8倍以上,且對(duì)TBA-354同時(shí)發(fā)生交叉耐藥。測(cè)序結(jié)果顯示fgd1基因未發(fā)生突變,但5株均檢測(cè)到ddn基因突變。耐藥株在無(wú)藥固體培養(yǎng)基上連續(xù)傳代10代后,MIC值無(wú)明顯變化。結(jié)論通過二倍遞增體外誘導(dǎo)可以獲得對(duì)2種硝基咪唑類(nitroimidazoles)藥物均耐藥的MTB菌株;MTB對(duì)硝基咪唑類藥物的耐藥可能與ddn基因突變有關(guān);MTB對(duì)硝基咪唑類藥物的耐藥穩(wěn)定性較強(qiáng),不易復(fù)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(xué)附屬北京胸科醫(yī)院北京市結(jié)核病胸部腫瘤研究所;
【基金】：國(guó)家科技新藥創(chuàng)制重大專項(xiàng)子課題(No.2015ZX09102007-015) 北京市醫(yī)院管理局臨床醫(yī)學(xué)發(fā)展專項(xiàng)經(jīng)費(fèi)資助(No.ZYLX201304)
【分類號(hào)】：R446.5

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