Cell envelope of bacteria producing glycopeptide antibiotics

产生糖肽抗生素的细菌的细胞被膜

• 批准号: 5434391
• 负责人: Professor Dr. Wolfgang Wohlleben
• 金额: --
• 依托单位: Lehrstuhl für Mikrobiologie / Biotechnologie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2004
• 资助国家: 德国
• 起止时间: 2003-12-31 至 2006-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5434391?language=en
• 关键词: Cell; envelope; bacteria; producing; glycopeptide

Glycopeptide antibiotics inhibit the synthesis of the bacterial cell wall by blocking the transpeptidation and transglycosylation. The resistance mechanism in most pathogens against glycopeptides involves the synthesis of alternative cell wall precursors. Due to the complexity of the resistance mechanism which comprises of at least three essential enzymes, it was expected that glycopeptide producers are the evolutionary origin of the resistance genes. However, none of the essential resistance genes was found in the antibiotic biosynthesis gene clusters of the producing Amycolatopsis species. The only functions which are localised in the cluster and may be related to resistance are a putative ABC-transporter, as well as a two component regulatory system and a carboxypeptidase. The latter have counterparts on vancomycin resistance transposons, but are dispensable for expressing resistance. The proposed research should answer the following questions: * How does the producer protect its cell wall from the action of its antibiotic? * How are the accessory resistance genes involved in resistance? * Are different cell wall precursors synthesized during exponential and stationary (=production) phase and how is their synthesis regulated? This will be analysed by mutation and overexpression studies of the putative resistance genes. The genes encoding the synthesis of the "normal" cell wall will be isolated and characterised. The regulation of the genes as well as the synthesis of the proteins will be investigated, with respect to co-regulation of resistance and antibiotic production. Furthermore, we plan to study the chemical structure of the murein precursors at different time points and in the mutants (cooperation with chemistry).

糖肽抗生素通过阻断过肽和过糖基化来抑制细菌细胞壁的合成。大多数病原体对糖肽的抗性机制涉及替代细胞壁前体的合成。由于耐药机制的复杂性，包括至少三种必需酶，因此预计糖肽生产剂是抗性基因的进化起源。然而，在产生杏仁核种类的抗生素生物合成基因簇中没有任何必要的抗性基因。群集中局部局部唯一与电阻有关的功能是推定的ABC转运蛋白，以及两个组件调节系统和羧肽酶。后者在万古霉素耐药性转座子上有对应物，但对于表达抗性是可分配的。拟议的研究应回答以下问题： *生产者如何保护其细胞壁免受其抗生素的作用？ *辅助抗性基因如何涉及抗性？ *是否在指数和固定（=生产）相中合成不同的细胞壁前体？如何调节其合成？这将通过对推定抗性基因的突变和过表达研究来分析。编码“正常”细胞壁合成的基因将被分离和表征。将研究基因的调节以及蛋白质的合成，以抗药性和抗生素产生的共同调节。此外，我们计划在不同时间点和突变体（与化学合作）中研究Murein前体的化学结构。