Origins Centre, Groningen, the Netherlands.
Department of Supramolecular & Biomaterials Chemistry, Leiden Institute of Chemistry, Leiden Universitygrid.5132.5grid.10419.3dgrid.5132.5, Leiden, the Netherlands.
Microbiol Spectr. 2022 Aug 31;10(4):e0169322. doi: 10.1128/spectrum.01693-22. Epub 2022 Jul 14.
Fusion of cells is an important and common biological process that leads to the mixing of cellular contents and the formation of multinuclear cells. Cell fusion occurs when distinct membranes are brought into proximity of one another and merge to become one. Fusion holds promise for biotechnological innovations, for instance, for the discovery of urgently needed new antibiotics. Here, we used antibiotic-producing bacteria that can proliferate without their cell wall as a model to investigate cell-cell fusion. We found that fusion between genetically distinct cells yields heterokaryons that are viable, contain multiple selection markers, and show increased antimicrobial activity. The rate of fusion induced using physical and chemical methods was dependent on membrane fluidity, which is related to lipid composition as a function of cellular age. Finally, by using an innovative system of synthetic membrane-associated lipopeptides, we achieved targeted fusion between distinctly marked cells to further enhance fusion efficiency. These results provide a molecular handle to understand and control cell-cell fusion, which can be used in the future for the discovery of new drugs. Cell-cell fusion is instrumental in introducing different sets of genes in the same environment, which subsequently leads to diversity. There is need for new protocols to fuse cells of different types together for biotechnological applications like drug discovery. We present here wall-deficient cells as a platform for the same. We identify the fluidity of the membrane as an important characteristic for the process of fusion. We demonstrate a cell-specific approach for fusion using synthetically designed peptides yielding cells with modified antibiotic production profiles. Overall, wall-deficient cells can be a chassis for innovative metabolite production by providing an alternative method for cell-cell fusion.
细胞融合是一种重要且常见的生物学过程，它导致细胞内容物的混合和多核细胞的形成。当不同的膜彼此靠近并融合成一个时，就会发生细胞融合。细胞融合为生物技术创新带来了希望，例如发现急需的新抗生素。在这里，我们使用可以在没有细胞壁的情况下增殖的产生抗生素的细菌作为模型来研究细胞-细胞融合。我们发现，遗传上不同的细胞之间的融合产生了杂种核，这些杂种核是有活力的，含有多个选择标记，并显示出增强的抗微生物活性。使用物理和化学方法诱导的融合率取决于膜流动性，而膜流动性与脂质组成有关，是细胞年龄的函数。最后，通过使用创新的合成膜相关脂肽系统，我们实现了明显标记的细胞之间的靶向融合，进一步提高了融合效率。这些结果为理解和控制细胞-细胞融合提供了一个分子手段，可以在未来用于发现新药物。细胞-细胞融合对于在相同环境中引入不同的基因集至关重要，这随后导致了多样性。需要有新的方案将不同类型的细胞融合在一起，用于药物发现等生物技术应用。我们在这里提出缺乏细胞壁的细胞作为相同的平台。我们确定膜的流动性是融合过程的一个重要特征。我们使用合成设计的肽展示了一种细胞特异性融合方法，得到了具有改良抗生素产生谱的细胞。总的来说，缺乏细胞壁的细胞可以作为创新代谢产物生产的底盘，为细胞-细胞融合提供一种替代方法。
