Das Transkriptionsnetzwerk der sigma S-vermittelten generellen Streßantwort in Escherichia coli: Promotorstrukturen, Netzwerkarchitektur und Verbindungen zu anderen globalen Netzwerken

• Applicant: Professorin Dr. Regine Hengge
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms
• Term: from 2002 to 2007
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5375409

Final Report Abstract

Our comprehensive identification of the a5 regulon not only clarified its major importance for the overall E.coli physiology (with cr5 controlling in fact around 10 % of the E.coli genes), but also revealed an extremely complex secondary regulation within the o5 regulon, indicating that 0s is in fact the master regulator of a huge regulatory network. With the regulatory cascades controlling (i) biofilm functions such as curli and cellulose biosynthesis, and (ii) the acid stress tolerance module, we analyzed two systems within the a5 network that will become paradigms for the regulatory logics of multiple feedforward cascades in general. Moreover, our finding that a number of GGDEF and EAL genes involved in the control of the novel signaling molecule c-di-GMP are under 0s control, places the inverse coordination of motility and adhesion/biofilm functions by c-di-GMP into the context of the general stress response, and opens the field for now analyzing the molecular and physiological functions of the many GGDEF and EAL genes in detail. Furthermore, our continuing analyses of the connections between the a5 network and the global regulatory systems operated by cAMP-CRP and the ArcB/ArcA two-component system have been the first to provide details both of direct communication of these systems at the levels of the respective master regulators as well as by cooperation of the master regulators at the level of downstream target gene expression. Finally, in this project we have systematically combined genomic methodology, which provides all genome-inclusive knowledge about regulatory dependencies of target genes, with careful molecular biology approaches directed towards understanding the control of key regulatory genes at all hierarchical levels of the cellular regulatory network. Moreover, we have integrated quantitative data about transcriptional and post-transcriptional regulation of key control systems. As demonstrated here, this comprehensive approach does not only allow the understanding of large and complex regulatory networks, but it will also become the basis of a future quantitative analysis and simulation both in vivo and in silico of complex systems behaviour.

Publications

• C. Pesavento, H. Weber, A. Possling, G. Tischendorf, and R. Hengge (2006) Cyclic-di- GMP-mediated signaling within the o5 network in Escherichia coli. FEMS Congress, Madrid, Spain, July 2006.
  
  
• Mika, F., and R. Hengge (2005) A two-component phosphotransfer network involving ArcB, ArcA and RssB coordinates synthesis and proteolysis of a5 in Escherichia coli. Genes Dev. 19, 2770-2781.
  
  
• Weber, H., A. Possling, and R. Hengge (2004) Genome-wide transcription and in-silico analysis of the general stress response network in Escherichia coli. Micro-Matrix Workshop on strategies to address anitmicrobial resistance through the exploitation of microbial genomics, Las Navas del Marquez, Spain.
  
  
• Weber, H., C. Pesavento, A. Possling, G. Tischendorf, and R. Hengge (2006) CycHc-diGMP signaling within the a5 network of Escherichia coli. Mol. Microbiol. 62, 1014- 1034 (Comment in Nature Rev. Microbiol. 4 (2006), 878-879). Reviews:
  
  
• Weber, H., C. Pesavento, A. Possling, G. Tischendorf, and R. Hengge (2006) Cyclic-di- GMP-mediated signaling within the 0s network in Escherichia coli. 158th Meeting of the Society of General Microbiology, University of Warwick, Great Britain, April 2006.
  
  
• Weber, H., C. Pesavento, A. Possling, G. Tischendorf, and R. Hengge (2006) Cyclic-di- GMP-mediated signaling within the os network in Escherichia coli. Gordon Research Conference on Microbial Stress Responses, Mount Holyoke College, MA, USA.
  
  
• Weber, H., C. Pesavento, A. Possling, G. Tischendorf, and R. Hengge (2006) Escherichia coli under stress: cyclic-di-GMP signaling within the a5 network. Workshop on Regulation of gene expression in bacteria and biodegradation of contaminants in the environment. Universidad Internacional de Andalucia, Baeza, Spain.
  
  
• Weber, H., T. Polen, J. Heuveling, V. Wendisch, and R. Hengge (2005) Genomewide analysis of the general stress response network in Escherichia coli: (/-dependent genes, promoters and sigma factor selectivity. J. Bacteriol. 187, 1591-1603.