Maaß Sandra, Otto Andreas, Albrecht Dirk, Riedel Katharina, Trautwein-Schult Anke, Becher Dörte
Institute of Microbiology, Department of Microbial Proteomics, University of Greifswald, Felix-Hausdorff-Str. 8, 17489 Greifswald, Germany.
Institute of Microbiology, Department of Microbial Physiology and Molecular Biology, University of Greifswald, Felix-Hausdorff-Str. 8, 17489 Greifswald, Germany.
Cells. 2018 Nov 15;7(11):213. doi: 10.3390/cells7110213.
The anaerobic pathogen is of growing significance for the health care system due to its increasing incidence and mortality. As infection is both supported and treated by antibiotics, a deeper knowledge on how antimicrobial agents affect the physiology of this important pathogen may help to understand and prevent the development and spreading of antibiotic resistant strains. As the proteomic response of a cell to stress aims at counteracting the harmful effects of this stress, it can be expected that the pattern of a pathogen's responses to antibiotic treatment will be dependent on the antibiotic mechanism of action. Hence, every antibiotic treatment is expected to result in a specific proteomic signature characterizing its mode of action. In the study presented here, the proteomic response of 630∆ to vancomycin, metronidazole, and fidaxomicin stress was investigated on the level of protein abundance and protein synthesis based on 2D PAGE. The quantification of 425 proteins of allowed the deduction of proteomic signatures specific for each drug treatment. Indeed, these proteomic signatures indicate very specific cellular responses to each antibiotic with only little overlap of the responses. Whereas signature proteins for vancomycin stress fulfil various cellular functions, the proteomic signature of metronidazole stress is characterized by alterations of proteins involved in protein biosynthesis and protein degradation as well as in DNA replication, recombination, and repair. In contrast, proteins differentially expressed after fidaxomicin treatment can be assigned to amino acid biosynthesis, transcription, cell motility, and the cell envelope functions. Notably, the data provided by this study hint also at so far unknown antibiotic detoxification mechanisms.
由于厌氧性病原体的发病率和死亡率不断上升，其对医疗保健系统的重要性日益凸显。由于感染既受到抗生素的支持，也通过抗生素进行治疗，因此更深入地了解抗菌药物如何影响这种重要病原体的生理学，可能有助于理解和预防抗生素耐药菌株的产生和传播。由于细胞对压力的蛋白质组学反应旨在抵消这种压力的有害影响，可以预期病原体对抗生素治疗的反应模式将取决于抗生素的作用机制。因此，每种抗生素治疗都有望产生一种特定的蛋白质组学特征，以表征其作用方式。在本研究中，基于二维聚丙烯酰胺凝胶电泳（2D PAGE），在蛋白质丰度和蛋白质合成水平上研究了630∆对万古霉素、甲硝唑和非达霉素应激的蛋白质组学反应。对425种蛋白质的定量分析使得能够推断出每种药物治疗特有的蛋白质组学特征。事实上，这些蛋白质组学特征表明细胞对每种抗生素的反应非常特异，反应之间只有很少的重叠。万古霉素应激的特征蛋白具有多种细胞功能，而甲硝唑应激的蛋白质组学特征则表现为参与蛋白质生物合成、蛋白质降解以及DNA复制、重组和修复的蛋白质发生改变。相比之下，非达霉素治疗后差异表达的蛋白质可归类为氨基酸生物合成、转录、细胞运动和细胞包膜功能。值得注意的是，本研究提供的数据还暗示了迄今未知的抗生素解毒机制。
