Bio-Sciences R&D Division, TCS Innovation Labs, Tata Consultancy Services Ltd., 54-B, Hadapsar Industrial Estate, Pune 411013, Maharashtra, India.
Present address: Novartis Healthcare Pvt. Ltd., #6 Raheja Mindspace, Hitec-city, Hyderabad 500081, India.
Gut Pathog. 2013 Sep 30;5(1):28. doi: 10.1186/1757-4749-5-28.
Three pathogenicity islands, viz. SPI-1 (Salmonella pathogenicity island 1), SPI-2 (Salmonella pathogenicity island 2) and T6SS (Type VI Secretion System), present in the genome of Salmonella typhimurium have been implicated in the virulence of the pathogen. While the regulation of SPI-1 and SPI-2 (both encoding components of the Type III Secretion System - T3SS) are well understood, T6SS regulation is comparatively less studied. Interestingly, inter-connections among the regulatory elements of these three virulence determinants have also been suggested to be essential for successful infection. However, till date, an integrated view of gene regulation involving the regulators of these three secretion systems and their cross-talk is not available.
In the current study, relevant regulatory information available from literature have been integrated into a single Boolean network, which portrays the dynamics of T3SS (SPI-1 and SPI-2) and T6SS mediated virulence. Some additional regulatory interactions involving a two-component system response regulator YfhA have also been predicted and included in the Boolean network. These predictions are aimed at deciphering the effects of osmolarity on T6SS regulation, an aspect that has been suggested in earlier studies, but the mechanism of which was hitherto unknown. Simulation of the regulatory network was able to recreate in silico the experimentally observed sequential activation of SPI-1, SPI-2 and T6SS.
The present study integrates relevant gene regulatory data (from literature and our prediction) into a single network, representing the cross-communication between T3SS (SPI-1 and SPI-2) and T6SS. This holistic view of regulatory interactions is expected to improve the current understanding of pathogenesis of S. typhimurium.
鼠伤寒沙门氏菌基因组中存在三个致病性岛，即 SPI-1（沙门氏菌致病性岛 1）、SPI-2（沙门氏菌致病性岛 2）和 T6SS（六型分泌系统），这些都与病原体的毒力有关。尽管 SPI-1 和 SPI-2（均编码 III 型分泌系统的组成部分 - T3SS）的调控已得到很好的理解，但 T6SS 的调控研究相对较少。有趣的是，这三个毒力决定因素的调控元件之间的相互联系也被认为对于成功感染是必不可少的。然而，迄今为止，涉及这三个分泌系统的调控因子及其串扰的基因调控综合视图尚不可用。
在当前的研究中，从文献中整合了相关的调控信息到一个单一的布尔网络中，描绘了 T3SS（SPI-1 和 SPI-2）和 T6SS 介导的毒力的动态。还预测并包含了一些涉及双组分系统响应调节剂 YfhA 的额外调控相互作用。这些预测旨在破译渗透压对 T6SS 调控的影响，这在早期研究中已经提出，但机制尚不清楚。对调控网络的模拟能够在计算机上重现实验观察到的 SPI-1、SPI-2 和 T6SS 的顺序激活。
本研究将相关的基因调控数据（来自文献和我们的预测）整合到一个单一的网络中，代表了 T3SS（SPI-1 和 SPI-2）和 T6SS 之间的交叉通讯。这种对调控相互作用的整体观点有望提高对鼠伤寒沙门氏菌发病机制的现有理解。
