Proteomic analysis of a NAP1 Clostridium difficile clinical isolate resistant to metronidazole.
Proteomic analysis of a NAP1 Clostridium difficile clinical isolate resistant to metronidazole.
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DOI：
10.1371/journal.pone.0082622
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Canadian Nosocomial Infection Surveillance Program (CNISP)
中科院分区：
文献类型：
--
作者：
Chong PM;Lynch T;McCorrister S;Kibsey P;Miller M;Gravel D;Westmacott GR;Mulvey MR;Canadian Nosocomial Infection Surveillance Program (CNISP)
艰难梭菌是一种厌氧的革兰氏阳性细菌，被认为是腹泻相关性腹泻的主要原因。甲硝唑是目前治疗轻中度丙型肝炎的一线药物。艰难感染。本实验室分离到一株C.对甲硝唑具有稳定耐药表型的艰难梭菌。鸟枪蛋白质组学方法被用来比较甲硝唑耐药和敏感菌株的蛋白质组差异。NAP1 C.艰难梭菌菌株CD26A54_R（Met抗性）、CD26A54_S（降低的敏感性）和VLOO 13（Met敏感性）生长至对数中期，并以低于MIC 2倍稀释度的浓度掺入甲硝唑。用iTRAQ标记来自每个样品的肽，并进行2D-LC-MS/MS分析。在没有甲硝唑的情况下，观察到C.艰难梭菌菌株CD26A54_S和CD26A54_R可能与甲硝唑敏感性或耐药性降低有关，包括DNA修复蛋白、推定的硝基还原酶和铁摄取调节因子（Fur）。甲硝唑治疗后，在所有菌株中的应激相关蛋白的表达中度增加。在CD26A54_R中还观察到DNA修复蛋白RecA的表达中度增加。本研究提供了一个深入的蛋白质组学分析的稳定，甲硝唑耐药的C。艰难分离株。结果提示，甲硝唑高水平耐药可能与多因素反应有关。艰难梭菌，包括改变铁代谢和/或DNA修复的可能作用。
Clostridium difficile is an anaerobic, Gram-positive bacterium that has been implicated as the leading cause of antibiotic-associated diarrhea. Metronidazole is currently the first-line treatment for mild to moderate C. difficile infections. Our laboratory isolated a strain of C. difficile with a stable resistance phenotype to metronidazole. A shotgun proteomics approach was used to compare differences in the proteomes of metronidazole-resistant and -susceptible isolates. NAP1 C. difficile strains CD26A54_R (Met-resistant), CD26A54_S (reduced- susceptibility), and VLOO13 (Met-susceptible) were grown to mid-log phase, and spiked with metronidazole at concentrations 2 doubling dilutions below the MIC. Peptides from each sample were labeled with iTRAQ and subjected to 2D-LC-MS/MS analysis. In the absence of metronidazole, higher expression was observed of some proteins in C. difficile strains CD26A54_S and CD26A54_R that may be involved with reduced susceptibility or resistance to metronidazole, including DNA repair proteins, putative nitroreductases, and the ferric uptake regulator (Fur). After treatment with metronidazole, moderate increases were seen in the expression of stress-related proteins in all strains. A moderate increase was also observed in the expression of the DNA repair protein RecA in CD26A54_R. This study provided an in-depth proteomic analysis of a stable, metronidazole-resistant C. difficile isolate. The results suggested that a multi-factorial response may be associated with high level metronidazole-resistance in C. difficile, including the possible roles of altered iron metabolism and/or DNA repair.
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影响因子：
5.2
作者：
Diniz, CG;Farias, LM;Smith, CJ
通讯作者：
Smith, CJ
影响因子：
5.2
作者：
Baines, Simon D.;O'Connor, Rachael;Wilcox, Mark H.
通讯作者：
Wilcox, Mark H.
DOI：
10.1006/bbrc.1997.7050
发表时间：
1997-07-30
影响因子：
3.1
作者：
Chang, KC;Ho, SW;Wang, JT
通讯作者：
Wang, JT
影响因子：
3
作者：
Emerson, Jenny E.;Stabler, Richard A.;Fairweather, Neil F.
通讯作者：
Fairweather, Neil F.
影响因子：
4.9
作者：
Alauzet, C.;Mory, F.;Lozniewski, A.
通讯作者：
Lozniewski, A.