Jain Kirti, Pradhan Amit, Mokashi Chaitanya, Saini Supreet
Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai, 400076 Maharashtra India.
Syst Synth Biol. 2015 Jun;9(1-2):19-31. doi: 10.1007/s11693-015-9160-3. Epub 2015 Feb 4.
Flagellar assembly in Salmonella is controlled by an intricate genetic and biochemical network. This network comprises of a number of inter-connected feedback loops, which control the assembly process dynamically. Critical among these are the FliA-FlgM feedback, FliZ-mediated positive feedback, and FliT-mediated negative feedback. In this work, we develop a mathematical model to track the dynamics of flagellar gene expression in Salmonella. Analysis of our model demonstrates that the network is wired to not only control the transition of the cell from a non-flagellated to a flagellated state, but to also control dynamics of gene expression during cell division. Further, we predict that FliZ encoded in the flagellar regulon acts as a critical secretion-dependent molecular link between flagella and Salmonella Pathogenicity Island 1 gene expression. Sensitivity analysis of the model demonstrates that the flagellar regulatory network architecture is extremely robust to mutations.
沙门氏菌中的鞭毛组装由一个复杂的遗传和生化网络控制。该网络由许多相互连接的反馈回路组成,这些回路动态地控制组装过程。其中关键的是FliA-FlgM反馈、FliZ介导的正反馈和FliT介导的负反馈。在这项工作中,我们开发了一个数学模型来追踪沙门氏菌中鞭毛基因表达的动态变化。对我们模型的分析表明,该网络不仅用于控制细胞从无鞭毛状态到有鞭毛状态的转变,还用于控制细胞分裂过程中的基因表达动态。此外,我们预测鞭毛调节子中编码的FliZ作为鞭毛与沙门氏菌致病岛1基因表达之间关键的分泌依赖性分子联系。模型的敏感性分析表明,鞭毛调节网络结构对突变具有极强的鲁棒性。