Molecular mechanisms of mycobacteria exit from their host cell

分枝杆菌退出宿主细胞的分子机制

• 批准号: 190972711
• 负责人: Dr. Monica Hagedorn
• 金额: --
• 依托单位: HMU Research, Development und Innovation gGmbH (HMU RDI)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/190972711?language=en
• 关键词: Molecular; mechanisms; mycobacteria; exit; their

Better knowledge about their virulence mechanisms and host cell interactions are indispensable to identify new therapy targets and develop new drugs to efficiently treat destructive mycobaterial infections, like tuberculosis caused by M. tuberculosis. Making use of the tractable Dictyostelium discoideum - M. marinum model system we have characterized cell-to-cell transmission via the F-actin based ejectosome structure. Most strikingly, with the initial help of correlative light and electronmicroscopy (CLEM) we could show show that the autophagic machinery is essential in successfull transmission of bacteria. In the proposed projects we want to continue the dissection of molecular players that lead to the generation and efficient function of ejectosomes. In addition, we will further characterize the role of autophagy in bacterial egress and follow the hypothesis that this might represent an evolutionary conserved mechanism of repairing large plasma-membrane wounds.

更好地了解它们的毒力机制和宿主细胞相互作用对于确定新的治疗目标和开发有效治疗破坏性支原体感染的新药是必不可少的，例如由结核分枝杆菌引起的结核病。利用易处理的盘基网柄菌-海洋分枝杆菌模型系统，我们研究了基于F-肌动蛋白的顶体结构在细胞间的传递。最引人注目的是，在相关光学和电子显微镜(CLEM)的初步帮助下，我们可以证明自噬机制在细菌的成功传播中是必不可少的。在拟议的项目中，我们希望继续剖析导致弹射体产生和有效功能的分子玩家。此外，我们将进一步描述自噬在细菌外泄中的作用，并遵循这样的假设，即这可能代表了修复大型质膜伤口的进化保守机制。

项目成果

The ESCRT and autophagy machineries cooperate to repair ESX-1-dependent damage at the Mycobacterium-containing vacuole but have opposite impact on containing the infection

• DOI: 10.1371/journal.ppat.1007501
• 发表时间: 2018-12-01
• 期刊: PLOS PATHOGENS
• 影响因子: 6.7
• 作者: Lopez-Jimenez, Ana T.;Cardenal-Munoz, Elena;Soldati, Thierry
• 通讯作者: Soldati, Thierry

The autophagic machinery ensures nonlytic transmission of mycobacteria

• DOI: 10.1073/pnas.1423318112
• 发表时间: 2015-02-17
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Gerstenmaier, Lilli;Pilla, Rachel;Hagedorn, Monica
• 通讯作者: Hagedorn, Monica