Understanding the sequential activation of Type III and Type VI Secretion Systems in Salmonella typhimurium using Boolean modeling

Gut Pathogens

Sharmila S Mande¹  Hannah Rajasingh²  Anirban Dutta¹  Chandrani Das¹ 

[1] 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

关键词: Cross-talk network;    Boolean modeling;    Type VI Secretion System (T6SS);    SPI-2;    Salmonella pathogenicity island 1 (SPI-1);    Salmonella typhimurium;   

Others  :  821016
DOI  :  10.1186/1757-4749-5-28

 received in 2013-07-16, accepted in 2013-09-14,  发布年份 2013

【 摘 要 】

Background

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2013 Das et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

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