Lehrstuhl für Analytische Chemie, Biomolekulare Massenspektrometrie, Fakultät für Chemie und Biochemie, Ruhr-Universität Bochum, Universitaetsstr. 150, 44780, Bochum, Germany.
J Biol Inorg Chem. 2010 Nov;15(8):1293-303. doi: 10.1007/s00775-010-0689-z. Epub 2010 Jul 25.
Multiresistant bacteria are becoming more and more widespread. It is therefore necessary to have new compound groups in hand, such as small cationic peptides, to cope with these challenges. In this work, we present a comprehensive approach by monitoring protein expression profiles in a gram-positive bacterium (Corynebacterium glutamicum) to investigate the cellular response to such a compound, a ferrocene-conjugated arginine- and tryptophan-rich pentapeptide. To achieve this, a proteomic outline was performed where the compound-treated sample was compared with an untreated control. This study comprises more than 900 protein identifications, including numerous integral membrane proteins, and among these 185 differential expressions. Surprisingly, unregulated catalase and no elevated H(2)O(2) levels demonstrate that no oxidative stress occurs after treatment with the iron-containing compound as a consequence of the potential Fenton reaction. A sufficient iron supply is evidenced by the iron-containing protein aconitase and SufB (the latter belongs to an iron-sulfur cluster assembly system) and decreased levels of ATP-binding-cassette-type cobalamin/Fe(3+) siderophore transporters. The organometallic peptide antibiotic targets the cell membrane, which is evident by decreased levels of various integral membrane proteins, such as peptide permeases and transporters, and an altered lipid composition. Conversion to a more rigid cell membrane seems to be a relevant protective strategy of C. glutamicum against the ferrocene-conjugated antimicrobial peptide compound.
耐药菌的出现变得越来越普遍。因此，我们需要掌握新的化合物群体，如小阳离子肽，以应对这些挑战。在这项工作中，我们通过监测革兰氏阳性菌（谷氨酸棒杆菌）中的蛋白质表达谱，提出了一种全面的方法，以研究该化合物（一种与二茂铁偶联的精氨酸和色氨酸丰富的五肽）对细胞的影响。为此，我们进行了蛋白质组学研究，将处理过的化合物样本与未经处理的对照样本进行了比较。这项研究包括了 900 多种蛋白质的鉴定，其中包括许多整合膜蛋白，在这些蛋白质中有 185 种表达水平存在差异。令人惊讶的是，未调节的过氧化氢酶和没有升高的 H2O2 水平表明，由于潜在的芬顿反应，铁化合物处理后不会发生氧化应激。含铁蛋白 aconitase 和 SufB（后者属于铁硫簇组装系统）以及 ATP 结合盒型钴胺素/Fe3+ 铁载体转运蛋白水平的降低表明存在充足的铁供应。该金属有机肽抗生素靶向细胞膜，这一点可以从各种整合膜蛋白（如肽渗透酶和转运蛋白）的水平降低以及脂类组成的改变得到证明。向更刚性的细胞膜的转化似乎是谷氨酸棒杆菌对二茂铁偶联抗菌肽化合物的一种相关保护策略。
