Department of Chemical Engineering, Indian Institute of Technology Bombay, Mumbai, India.
Bio-Sciences R&D Division, TCS Research, Tata Consultancy Services Limited, Pune, India.
Front Cell Infect Microbiol. 2018 Feb 8;8:36. doi: 10.3389/fcimb.2018.00036. eCollection 2018.
The food-borne pathogen is a common cause of infections and diseases in a wide range of hosts. One of the major virulence factors associated to the infection process is flagella, which helps the bacterium swim to its preferred site of infection inside the host, the M-cells (Microfold cells) lining the lumen of the small intestine. The expression of flagellar genes is controlled by an intricate regulatory network. In this work, we investigate two aspects of flagella regulation and assembly: (a) distribution of the number of flagella in an isogenic population of bacteria and (b) dynamics of gene expression post cell division. More precisely, in a population of bacteria, we note a normal distribution of number of flagella assembled per cell. How is this distribution controlled, and what are the key regulators in the network which help the cell achieve this? In the second question, we explore the role of protein secretion in dictating gene expression dynamics post cell-division (when the number of hook basal bodies on the cell surface is reduced by a factor of two). We develop a mathematical model and perform stochastic simulations to address these questions. Simulations of the model predict that two accessory regulators of flagella gene expression, FliZ and FliT, have significant roles in maintaining population level distribution of flagella. In addition, FliT and FlgM were predicted to control the level and temporal order of flagellar gene expression when the cell adapts to post cell division consequences. Further, the model predicts that, the FliZ and FliT dependent feedback loops function under certain thresholds, alterations in which can substantially affect kinetics of flagellar genes. Thus, based on our results we propose that, the proteins FlgM, FliZ, and FliT, thought to have accessory roles in regulation of flagella, likely play a critical role controlling gene expression during cell division, and frequency distribution of flagella.
食源性病原体是广泛宿主感染和疾病的常见原因。与感染过程相关的主要毒力因子之一是鞭毛，它帮助细菌游向其在宿主中的首选感染部位，即小肠腔衬里的 M 细胞（微褶细胞）。鞭毛基因的表达受复杂的调控网络控制。在这项工作中，我们研究了鞭毛调节和组装的两个方面：（a）在细菌的同基因群体中鞭毛数量的分布，以及（b）细胞分裂后基因表达的动力学。更确切地说，在细菌群体中，我们注意到每个细胞组装的鞭毛数量呈正态分布。这种分布是如何控制的，网络中的关键调节剂是什么，帮助细胞实现这一点？在第二个问题中，我们探讨了蛋白质分泌在决定细胞分裂后基因表达动力学中的作用（当细胞表面钩基底体的数量减少一半时）。我们开发了一个数学模型并进行了随机模拟来解决这些问题。模型模拟预测，鞭毛基因表达的两个辅助调节剂，FliZ 和 FliT，在维持群体水平鞭毛分布方面具有重要作用。此外，当细胞适应细胞分裂后的后果时，预测 FliT 和 FlgM 控制着鞭毛基因表达的水平和时间顺序。此外，该模型预测，FliZ 和 FliT 依赖的反馈回路在一定阈值下起作用，其改变可能会极大地影响鞭毛基因的动力学。因此，根据我们的结果，我们提出，FlgM、FliZ 和 FliT 蛋白被认为在鞭毛调节中具有辅助作用，可能在细胞分裂过程中以及鞭毛的基因表达和频率分布中起着关键作用。
