From primary target inhibition to collapse of the cell envelope biosynthetic network (A10)

从主要靶标抑制到细胞包膜生物合成网络崩溃 (A10)

• 批准号: 425789108
• 金额: --
• 依托单位: Arbeitsgruppe Pharmazeutische Mikrobiologie
• 依托单位国家: 德国
• 项目类别: CRC/Transregios
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/425789108?language=en
• 关键词: primary; target; inhibition; collapse; cell

Targeting the peptidoglycan precursor lipid II can induce multifactorial cellular effects that go beyond sequestration of the cell wall building block. Teixobactin and related antibiotics target multiple undecaprenyl-coupled lipid intermediates, induce strong lysis and form supramolecular structures upon target interaction. They also have a limited potential for resistance development. We will dissect the cellular signatures induced by teixobactin and teixobactin-like antibiotics and compare these to other cell wall targeting antibiotics. The aim is to unravel on the cellular and molecular level differential mechanisms that converge onto the collapse of highly interlinked cell wall biosynthetic networks.

靶向肽聚糖前体脂质II可以诱导多因子细胞效应，其超出细胞壁构建块的螯合。Teixobactin和相关抗生素靶向多个十一异戊二烯偶联的脂质中间体，诱导强烈的裂解，并在靶向相互作用后形成超分子结构。它们也具有有限的耐药性发展潜力。我们将剖析teixobactin和teixobactin样抗生素诱导的细胞特征，并将其与其他细胞壁靶向抗生素进行比较。其目的是解开细胞和分子水平的差异机制，收敛到高度互连的细胞壁生物合成网络的崩溃。