Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Mecklenburg-Vorpommern, Germany;; Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Institute of Bioinformatics, University Medicine Greifswald, Greifswald, Mecklenburg-Vorpommern, Germany.
Mol Cell Proteomics. 2019 May;18(5):892-908. doi: 10.1074/mcp.RA118.001138. Epub 2019 Feb 26.
is infamous for causing recurrent infections of the human respiratory tract. This is a consequence of its ability to adapt to different niches, including the intracellular milieu of lung epithelial cells. To understand the dynamic interplay between epithelial cells and the intracellular pathogen, we dissected their interactions over 4 days by mass spectrometry. Additionally, we investigated the dynamics of infection through live cell imaging, immunofluorescence and electron microscopy. The results highlight a major role of often overlooked temporal changes in the bacterial and host metabolism, triggered by fierce competition over limited resources. Remarkably, replicating bacteria reside predominantly within membrane-enclosed compartments and induce apoptosis of the host within ∼24 h post infection. Surviving infected host cells carry a subpopulation of non-replicating bacteria in the cytoplasm that persists. Altogether, we conclude that, besides the production of virulence factors by bacteria, it is the way in which intracellular resources are used, and how host and intracellular bacteria subsequently adapt to each other that determines the ultimate outcome of the infectious process.
它以引起人类呼吸道反复感染而臭名昭著。这是其适应不同生态位的能力的结果，包括肺上皮细胞的细胞内环境。为了了解上皮细胞和细胞内病原体之间的动态相互作用，我们通过质谱法在 4 天内对它们的相互作用进行了剖析。此外，我们通过活细胞成像、免疫荧光和电子显微镜研究了感染的动态。结果突出了细菌和宿主代谢中经常被忽视的时间变化的主要作用，这些变化是由对有限资源的激烈竞争引发的。值得注意的是，复制的细菌主要存在于膜封闭的隔室中，并在感染后约 24 小时内诱导宿主细胞凋亡。存活的受感染宿主细胞在细胞质中携带持续存在的非复制细菌的亚群。总的来说，我们的结论是，除了细菌产生毒力因子之外，决定感染过程最终结果的还有细胞内资源的利用方式，以及宿主和细胞内细菌随后如何相互适应。
