Computational modelling and analysis of the molecular network regulating sporulation initiation in Bacillus subtilis

BMC Systems Biology

Gary C Barker¹  Ivan Mura²  Adaoha EC Ihekwaba¹ 

[1] Gut Health and Food Safety, Institute of Food Research, Norwich Research Park, Colney, Norwich, UK;Faculty of Engineering, EAN University, Carrera 11 No. 78 – 47, Bogotá, Colombia

关键词: Bacillus subtilis;    Sporulation;    Signal transduction;    Sensitivity analysis;    Computational modelling;    Systems biology;   

Others  :  1091852
DOI  :  10.1186/s12918-014-0119-x

 received in 2014-08-08, accepted in 2014-10-13,  发布年份 2014

【 摘 要 】

Background

Bacterial spores are important contaminants in food, and the spore forming bacteria are often implicated in food safety and food quality considerations. Spore formation is a complex developmental process involving the expression of more than 500 genes over the course of 6 to 8 hrs. The process culminates in the formation of resting cells capable of resisting environmental extremes and remaining dormant for long periods of time, germinating when conditions promote further vegetative growth. Experimental observations of sporulation and germination are problematic and time consuming so that reliable models are an invaluable asset in terms of prediction and risk assessment. In this report we develop a model which assists in the interpretation of sporulation dynamics.

Results

This paper defines and analyses a mathematical model for the network regulating Bacillus subtilis sporulation initiation, from sensing of sporulation signals down to the activation of the early genes under control of the master regulator Spo0A. Our model summarises and extends other published modelling studies, by allowing the user to execute sporulation initiation in a scenario where Isopropyl β-D-1-thiogalactopyranoside (IPTG) is used as an artificial sporulation initiator as well as in modelling the induction of sporulation in wild-type cells. The analysis of the model results and the comparison with experimental data indicate that the model is good at predicting inducible responses to sporulation signals. However, the model is unable to reproduce experimentally observed accumulation of phosphorelay sporulation proteins in wild type B. subtilis. This model also highlights that the phosphorelay sub-component, which relays the signals detected by the sensor kinases to the master regulator Spo0A, is crucial in determining the response dynamics of the system.

Conclusion

We show that there is a complex connectivity between the phosphorelay features and the master regulatory Spo0A. Additional we discovered that the experimentally observed regulation of the phosphotransferase Spo0B for wild-type B. subtilis may be playing an important role in the network which suggests that modelling of sporulation initiation may require additional experimental support.

【 授权许可】

   
2014 Ihekwaba et al.; licensee BioMed Central Ltd.

【 图 表 】

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