泛素样蛋白蛋白酶体系统对单耐异烟肼结核分枝杆菌耐药性机制研究

发布时间：2018-06-12 10:42

本文选题：结核分枝杆菌 + 泛素样蛋白-蛋白酶体系统　；参考：《中国病原生物学杂志》2017年06期

【摘要】：目的探讨泛素样蛋白蛋白酶体系统对单耐异烟肼结核分枝杆菌耐药性的影响及其机制。方法采用刃天青显色法,比较单耐异烟肼结核分枝杆菌(对照组)与4种基因(Pup、Dop、PafA、Mpa基因)分别过表达和缺失单耐异烟肼结核分枝杆菌菌株异烟肼最低抑菌浓度(minimum inhibitory concentration,MIC)值的差异;比较加入改变细胞壁通透性试剂后,单耐异烟肼结核分枝杆菌(对照组)与4种基因分别过表达和缺失单耐异烟肼结核分枝杆菌菌株异烟肼MIC差值间的差异。结果 (1)与单耐异烟肼结核分枝杆菌相比,异烟肼的MIC值过表达PafA基因株增加1.03μg/ml,过表达Dop、Mpa基因株分别降低1.03μg/ml、0.68μg/ml,差异均无统计学意义(F=1.898,P0.05);过表达Pup基因株异烟肼的MIC值增加8μg/ml,差异有统计学意义(t=2.185,P0.05);缺失Pup、Dop、PafA、Mpa基因株异烟肼的MIC值分别降低4.82、4.98、4.99、4.9μg/ml,差异均有统计学意义(F=35.809,P0.05)。(2)与加入改变细胞壁通透性试剂后单耐异烟肼结核分枝杆菌相比,异烟肼的MIC差值过表达Pup基因株增加7.78μg/ml,差异有统计学意义(t=2.173,P0.05);缺失Pup、Dop、PafA、Mpa基因株分别降低4.58、4.73、4.75、4.68μg/ml,差异均有统计学意义(F=33.598,P0.05);过表达Dop、Mpa基因株分别降低1μg/ml和0.7μg/ml,过表达PafA基因株增加0.97μg/ml,差异均无统计学意义(F=1.935,P0.05)。结论结核分枝杆菌泛素样蛋白蛋白酶体系统可能通过调控单耐异烟肼结核分枝杆菌细胞壁的通透性影响其耐药性。
[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.
【作者单位】：石河子大学医学院病理生理学教研室新疆地方与民族高发病教育部重点实验室西部地区高发人兽共患传染性疾病防治协同创新中心;南京医科大学基础医学院;石河子大学医学院第一附属医院;
【基金】：国家自然科学基金项目(No.81260261) 石河子大学高层次人才科研启动项目(No.RCZX201446)
【分类号】：R378.911

【相似文献】