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泛素樣蛋白蛋白酶體系統(tǒng)對單耐異煙肼結(jié)核分枝桿菌耐藥性機制研究

發(fā)布時間:2018-06-12 10:42

  本文選題:結(jié)核分枝桿菌 + 泛素樣蛋白-蛋白酶體系統(tǒng); 參考:《中國病原生物學(xué)雜志》2017年06期


【摘要】:目的探討泛素樣蛋白蛋白酶體系統(tǒng)對單耐異煙肼結(jié)核分枝桿菌耐藥性的影響及其機制。方法采用刃天青顯色法,比較單耐異煙肼結(jié)核分枝桿菌(對照組)與4種基因(Pup、Dop、PafA、Mpa基因)分別過表達和缺失單耐異煙肼結(jié)核分枝桿菌菌株異煙肼最低抑菌濃度(minimum inhibitory concentration,MIC)值的差異;比較加入改變細胞壁通透性試劑后,單耐異煙肼結(jié)核分枝桿菌(對照組)與4種基因分別過表達和缺失單耐異煙肼結(jié)核分枝桿菌菌株異煙肼MIC差值間的差異。結(jié)果 (1)與單耐異煙肼結(jié)核分枝桿菌相比,異煙肼的MIC值過表達PafA基因株增加1.03μg/ml,過表達Dop、Mpa基因株分別降低1.03μg/ml、0.68μg/ml,差異均無統(tǒng)計學(xué)意義(F=1.898,P0.05);過表達Pup基因株異煙肼的MIC值增加8μg/ml,差異有統(tǒng)計學(xué)意義(t=2.185,P0.05);缺失Pup、Dop、PafA、Mpa基因株異煙肼的MIC值分別降低4.82、4.98、4.99、4.9μg/ml,差異均有統(tǒng)計學(xué)意義(F=35.809,P0.05)。(2)與加入改變細胞壁通透性試劑后單耐異煙肼結(jié)核分枝桿菌相比,異煙肼的MIC差值過表達Pup基因株增加7.78μg/ml,差異有統(tǒng)計學(xué)意義(t=2.173,P0.05);缺失Pup、Dop、PafA、Mpa基因株分別降低4.58、4.73、4.75、4.68μg/ml,差異均有統(tǒng)計學(xué)意義(F=33.598,P0.05);過表達Dop、Mpa基因株分別降低1μg/ml和0.7μg/ml,過表達PafA基因株增加0.97μg/ml,差異均無統(tǒng)計學(xué)意義(F=1.935,P0.05)。結(jié)論結(jié)核分枝桿菌泛素樣蛋白蛋白酶體系統(tǒng)可能通過調(diào)控單耐異煙肼結(jié)核分枝桿菌細胞壁的通透性影響其耐藥性。
[Abstract]:Objective to investigate the effect of ubiquitin like proteasome system on drug resistance of Mycobacterium tuberculosis with isoniazid resistance and its mechanism. Methods the difference of minimum inhibitory concentration and minimum inhibitory concentration of isoniazid resistant Mycobacterium tuberculosis (control group) and four genes (PupDopPafA Mpa) were compared by using the method of azure blue coloration, respectively, and the minimum inhibitory concentration of isoniazid was found in Mycobacterium tuberculosis strains with isoniazid resistance. The difference of MIC difference of isoniazid resistant Mycobacterium tuberculosis (control group) and four genes were compared after adding the reagent to change the permeability of cell wall. Results compared with Mycobacterium tuberculosis resistant to isoniazid, The MIC value of isoniazid over-expressed PafA gene strain increased 1.03 渭 g / ml, and the over-expressed DopMpa gene strain decreased 1.03 渭 g / ml 0.68 渭 g / ml, respectively. The difference was not statistically significant. The MIC value of isoniazid gene strain was increased by 8 渭 g / ml, the difference was statistically significant, and the absence of PupupDopPafAMpa gene strain was different from that of Pupup DopPafAMpa gene strain. The MIC values of niazid decreased by 4.82 渭 g / ml, 4.98 渭 g / ml and 4.98 渭 g / ml, respectively. The difference was statistically significant compared with that of Mycobacterium tuberculosis monoresistant to isoniazid after adding the reagent to change the permeability of cell wall. The mics difference of isoniazid overexpression Pup gene strain increased 7.78 渭 g / ml, the difference was statistically significant, and the PafA Mpa gene strain with missing PupDoppler gene decreased 4.58 渭 g / ml and 4.73 渭 g / ml, respectively, and the overexpression of DopMpa gene strain decreased 1 渭 g/ml and 0.7 渭 g / ml, respectively, and the overexpression of DopMpa gene strain decreased by 1 渭 g/ml and 0.7 渭 g / ml, respectively, and the expression of PafA gene strain increased by 4.58 渭 g / ml. 0.97 渭 g / ml, the difference was not statistically significant. Conclusion the Ubiquitin like proteasome system of Mycobacterium tuberculosis may influence its drug resistance by regulating the permeability of the cell wall of isoniazid resistant Mycobacterium tuberculosis.
【作者單位】: 石河子大學(xué)醫(yī)學(xué)院病理生理學(xué)教研室新疆地方與民族高發(fā)病教育部重點實驗室西部地區(qū)高發(fā)人獸共患傳染性疾病防治協(xié)同創(chuàng)新中心;南京醫(yī)科大學(xué)基礎(chǔ)醫(yī)學(xué)院;石河子大學(xué)醫(yī)學(xué)院第一附屬醫(yī)院;
【基金】:國家自然科學(xué)基金項目(No.81260261) 石河子大學(xué)高層次人才科研啟動項目(No.RCZX201446)
【分類號】:R378.911

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1 陳曦,馬s,

本文編號:2009394


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