Proteomic Analysis of Drug-Resistant Mycobacteria: Co-Evolution of Copper and INH Resistance.
Proteomic Analysis of Drug-Resistant Mycobacteria: Co-Evolution of Copper and INH Resistance.
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耐药分枝杆菌的蛋白质组学分析：铜和异烟肼耐药性的共同进化
DOI：
10.1371/journal.pone.0127788
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Deng H
中科院分区：
文献类型：
--
作者：
Chen Y;Yang F;Sun Z;Wang Q;Mi K;Deng H
结核病是由结核分枝杆菌引起的一种世界性公共卫生威胁。结核分枝杆菌能够抵抗宿主细胞中的各种压力，包括高水平的ROS和铜离子。为了更好地了解分枝杆菌对铜的抗性机制，我们从硫酸铜处理过的细菌中筛选出一株耻垢分枝杆菌耐铜菌株mc2155-Cu。Mc2155-Cu菌株对硫酸铜的抗性是其亲本菌株mc2155的5倍，对异烟肼(INH)的抗性是其亲本菌株的2倍。用定量蛋白质组学方法寻找mc2155和mc2155-Cu之间的差异表达蛋白质。在345个差异表达蛋白中，铜转运蛋白P型ATPase表达上调，而其他ABC转运蛋白在mc2155-Cu中低表达，提示铜转运蛋白P型ATPase在铜抗性中起重要作用。结果还表明，与mc2155相比，mc2155-Cu中代谢酶的下调以及细胞内NAD、FAD、霉菌硫醇和谷氨酰胺水平的降低是其生长速度放缓的原因。在蛋白和mRNA水平下调KatG2的表达，表明耐铜细菌对铜和异烟肼抗性的共同进化，为理解分枝杆菌在应激条件下生存的分子机制提供了新的证据。
Tuberculosis, caused by the pathogen Mycobacterium tuberculosis, is a worldwide public health threat. Mycobacterium tuberculosis is capable of resisting various stresses in host cells, including high levels of ROS and copper ions. To better understand the resistance mechanisms of mycobacteria to copper, we generated a copper-resistant strain of Mycobacterium smegmatis, mc2155-Cu from the selection of copper sulfate treated-bacteria. The mc2155-Cu strain has a 5-fold higher resistance to copper sulfate and a 2-fold higher resistance to isoniazid (INH) than its parental strain mc2155, respectively. Quantitative proteomics was carried out to find differentially expressed proteins between mc2155 and mc2155-Cu. Among 345 differentially expressed proteins, copper-translocating P-type ATPase was up-regulated, while all other ABC transporters were down-regulated in mc2155-Cu, suggesting copper-translocating P-type ATPase plays a crucial role in copper resistance. Results also indicated that the down-regulation of metabolic enzymes and decreases in cellular NAD, FAD, mycothiol, and glutamine levels in mc2155-Cu were responsible for its slowing growth rate as compared to mc2155. Down-regulation of KatG2 expression in both protein and mRNA levels indicates the co-evolution of copper and INH resistance in copper resistance bacteria, and provides new evidence to understanding of the molecular mechanisms of survival of mycobacteria under stress conditions.
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影响因子：
30.3
作者：
Samanovic MI;Ding C;Thiele DJ;Darwin KH
通讯作者：
Darwin KH
DOI：
10.1073/pnas.97.2.652
发表时间：
2000-01-18
影响因子：
11.1
作者：
Rensing, C;Fan, B;Rosen, BP
通讯作者：
Rosen, BP
DOI：
10.1073/pnas.1009261108
发表时间：
2011-01-25
影响因子：
11.1
作者：
Wolschendorf, Frank;Ackart, David;Niederweis, Michael
通讯作者：
Niederweis, Michael
影响因子：
11.3
作者：
Gengenbacher M;Kaufmann SH
通讯作者：
Kaufmann SH
影响因子：
2.8
作者：
Sitthisak, Sutthirat;Knutsson, Lawrence;Jayaswal, Radheshyam K.
通讯作者：
Jayaswal, Radheshyam K.