Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, United States of America.
PLoS One. 2011 Apr 20;6(4):e18877. doi: 10.1371/journal.pone.0018877.
The evolution of eukaryotic cells is widely agreed to have proceeded through a series of endosymbiotic events between larger cells and proteobacteria or cyanobacteria, leading to the formation of mitochondria or chloroplasts, respectively. Engineered endosymbiotic relationships between different species of cells are a valuable tool for synthetic biology, where engineered pathways based on two species could take advantage of the unique abilities of each mutualistic partner.
We explored the possibility of using the photosynthetic bacterium Synechococcus elongatus PCC 7942 as a platform for studying evolutionary dynamics and for designing two-species synthetic biological systems. We observed that the cyanobacteria were relatively harmless to eukaryotic host cells compared to Escherichia coli when injected into the embryos of zebrafish, Danio rerio, or taken up by mammalian macrophages. In addition, when engineered with invasin from Yersinia pestis and listeriolysin O from Listeria monocytogenes, S. elongatus was able to invade cultured mammalian cells and divide inside macrophages.
Our results show that it is possible to engineer photosynthetic bacteria to invade the cytoplasm of mammalian cells for further engineering and applications in synthetic biology. Engineered invasive but non-pathogenic or immunogenic photosynthetic bacteria have great potential as synthetic biological devices.
真核细胞的进化被广泛认为是通过较大细胞与变形菌或蓝细菌之间的一系列内共生事件发生的，分别导致了线粒体或叶绿体的形成。不同物种细胞之间的工程内共生关系是合成生物学的一种有价值的工具，基于两种物种的工程途径可以利用每个互利伙伴的独特能力。
我们探索了使用光合细菌集胞藻 PCC 7942 作为研究进化动态和设计两种生物合成系统的平台的可能性。我们观察到，与大肠杆菌相比，当将蓝细菌注射到斑马鱼、Danio rerio 的胚胎中或被哺乳动物巨噬细胞摄取时，蓝细菌对真核宿主细胞相对无害。此外，当用鼠疫耶尔森菌的侵袭蛋白和李斯特菌的李斯特菌素 O 进行工程改造后，集胞藻能够入侵培养的哺乳动物细胞并在巨噬细胞内分裂。
我们的结果表明，可以对光合细菌进行工程改造使其入侵哺乳动物细胞的细胞质，以便在合成生物学中进行进一步的工程设计和应用。经过工程改造的入侵但非致病性或免疫原性的光合细菌具有作为合成生物学器件的巨大潜力。
