Lee Tae J, Wong Jeffrey, Bae Sena, Lee Anna Jisu, Lopatkin Allison, Yuan Fan, You Lingchong
Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America; Center for Genomic and Computational Biology, Duke University, Durham, North Carolina, United States of America.
Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America.
PLoS Comput Biol. 2015 Apr 16;11(4):e1004203. doi: 10.1371/journal.pcbi.1004203. eCollection 2015 Apr.
Pathogenic bacteria such as Listeria and Yersinia gain initial entry by binding to host target cells and stimulating their internalization. Bacterial uptake entails successive, increasingly strong associations between receptors on the surface of bacteria and hosts. Even with genetically identical cells grown in the same environment, there are vast differences in the number of bacteria entering any given cell. To gain insight into this variability, we examined uptake dynamics of Escherichia coli engineered to express the invasin surface receptor from Yersinia, which enables uptake via mammalian host β1-integrins. Surprisingly, we found that the uptake probability of a single bacterium follows a simple power-law dependence on the concentration of integrins. Furthermore, the value of a power-law parameter depends on the particular host-bacterium pair but not on bacterial concentration. This power-law captures the complex, variable processes underlying bacterial invasion while also enabling differentiation of cell lines.
诸如李斯特菌和耶尔森氏菌等病原菌通过与宿主靶细胞结合并刺激其内化来实现最初的侵入。细菌摄取需要细菌表面受体与宿主之间连续且越来越强的关联。即使是在相同环境中生长的基因相同的细胞,进入任何给定细胞的细菌数量也存在巨大差异。为了深入了解这种变异性,我们研究了经基因工程改造以表达耶尔森氏菌侵袭素表面受体的大肠杆菌的摄取动力学,该受体可通过哺乳动物宿主β1整合素实现摄取。令人惊讶的是,我们发现单个细菌的摄取概率对整合素浓度呈现出简单的幂律依赖性。此外,幂律参数的值取决于特定的宿主 - 细菌对,而不取决于细菌浓度。这种幂律既捕捉了细菌入侵背后复杂多变的过程,同时也能够区分不同的细胞系。