Cluster:

UroGenOmics: Strain-specific systems biology of uropathogenic bacteria

Coordinator:
  • Prof. Dr. Dieter Jahn & Dr. Petra Tielen, Institut für Mikrobiologie, TU Braunschweig

Project Partners:
  • Prof. Dr. Ulrich Dobrindt, Institut für Hygiene, Universitätsklinikum Münster
  • Prof. Dr. Johannes Hübner, Infektiologie, Universitätsklinikum Freiburg
  • Prof. Dr. Rainer Krull,Institut für Bioverfahrenstechnik, TU Braunschweig
  • Dr. Richard Münch, Institut für Mikrobiologie, TU Braunschweig
  • Prof. Dr. Katharina Riedel, Institut für Mikrobiologie, TU Braunschweig Helmholtz Zentrum für Infektionsforschung, Braunschweig
  • Prof. Dr. Dietmar Schomburg, Institut für Biochemie und Biotechnologie, TU Braunschweig
  • Prof. Dr. Christoph Wittmann, Institut für Bioverfahrenstechnik, TU Braunschweig

Description:
In the framework of the program ´´Medizinische Infektionsgenomik´´ funded by the BMBF, the UroGenOmics consortium utilises a functional quantitative genomics approach to investigate the cellular processes, which play a central role for the development of chronic catheter-associated urinary tract infections.
Escherichia coli, Pseudomonas aeruginosa and Enterococcus faecalis are the leading bacterial pathogens of common human urinary tract and catheter-associated urinary tract infections. In contrast to their daily clinical importance and wide spread occurance, the basic molecular understanding of the genetic strategies successfully employed by these bacteria during the process of urinary tract uinfections is completely missing.
For the first time, the outlined consortium provides a high-end functional genomics analysis pipeline for the elucidation of strain-specific and consortia-related regulatory and metabolic strategies.
Genome sequences of several uropathogenic isolates are available. Based on the sequenced genomes a systematic characterization by transcriptome, proteome and metabolome analyses will be performed. Relevant gene regulatory circuits including small RNAs of selected representative strains will be targeted by DNA microarray approaches and cDNA sequencing in cooperation with the University Göttingen (PD Daniel). Quantitative analysis of involved proteomic networks will be performed by the group of Prof. Riedel (Technische Universität Braunschweig). Metabolome (Prof. Schomburg, Technische Universität Braunschweig) and fluxome data (Prof. Wittmann, Technische Universität Braunschweig) are closing the gap between regulatory and metabolic network analyses. Metaproteomics data (Prof. Riedel, Technische Universität Braunschweig) of the microbial biofilm communities from in vivo and in vitro catheter will be complete the picture. An established bioinformatics platform in Braunschweig with comprehensive databases and interpretation tools provides a solid basis for necessary data integration. Uropathogenetic specific expression profiles and metabolic networks will be deduced. For the analysis of single strain and reconstituted community biofilms, a catheter model was established (Prof. Krull, Technische Universität Braunschweig). Next to the growth of biofilms under infection-relevant conditions this reactor will be used for improving of new antimicrobial catheter surfaces designed in cooperation with the Fraunhofer IST and industry partners.
The deep understanding of these processes will be used to develop new therapy and avoiding strategies. Furthermore, new antimicrobial catheter surfaces will be developed and a novel diagnostic DNA-chip will be established, which not only gives information about the involved species, their resistance and virulence stectra but also about their general physiological status.



























Structure of the UroGenOmic consortium.
Green squares indicate groups of the consortium, blue squares show the participation of the various platforms. We are still in process to recruit a catheter manufactory company. The three uropathogens of interest and the microbial consortia are represented by the indicated groups. All is centred around the catheter model for growth. Catheter-grown bacteria and communities will be functionally characterized by indicated Omics technologies partly provided by the consortia (green) partly by the platforms (blue). Generated data are stored, analysed and integrated in the bioinformatics project. Comparative genomics is also a task of this group. Results are subsequently transferred into applications.

 
Structure of the UroGenOmic consortium.
Green squares indicate groups of the consortium, blue squares show the participation of the various platforms. We are still in process to recruit a catheter manufactory company. The three uropathogens of interest and the microbial consortia are represented by the indicated groups. All is centred around the catheter model for growth. Catheter-grown bacteria and communities will be functionally characterized by indicated Omics technologies partly provided by the consortia (green) partly by the platforms (blue). Generated data are stored, analysed and integrated in the bioinformatics project. Comparative genomics is also a task of this group. Results are subsequently transferred into applications.


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