Prof. Karin Schnetz

Institute for Genetics

Zuelpicher Str. 47a
Gebäude: 301
50674 Cologne

Role of LuxR-type transcription factors and H-NS in pathogenic Escherichia coli

Escherichia coli include commensal strains residing in the intestine of vertebrates and pathogenic strains which cause various intra- and extraintestinal diseases. The nucleoid-associated protein H-NS is a gobal repressor (silencer protein) in Enterobacteriaceae and a regulator of genes for pathogenicity, biofilm formation and stress responses. Repression by H-NS is relieved gene-specifically, and in most cases this involves specific transcription factors. Up to date little is known about transcription factors required for de-repression of pathogenicity genes and the signals and pathways activating them. We study transcription factors of the so-called LuxR-family which include ‘master’ regulators of pathogenicity genes.

In one project the role of selected LuxR-type transcription factors will be analyzed in commensal and pathogenic E. coli. The aims are: (i) to analyze the induction of the genes encoding the LuxR-type transcription factors, which will include co-cultivation of pathogenic E. coli with eukaryotic cell lines (with focus on uropathogens); (ii) to identify levels of post-translational control such as proteolysis and protein-protein interaction of the selected LuxR-type transcription factors; and (iii) to characterize the direct target genes of these LuxR-type transcription factors by genetic screens and by microarray analyses, followed by molecular analysis. The aim of the project is to identify novel regulatory signaling cascades in pathogenicity of E. coli.

In another project the mechanism of repression by H-NS and the role of transcription in de-repression will be addressed. H?NS represses transcription by formation of extended H-NS-DNA complexes, which prevent initiation of transcription by RNA polymerase. RNA polymerase, once it is engaged in transcription, is a powerful enzyme. Our unpublished data indicate that RNA polymerase when transcribing across H-NS nucleoprotein complexes remodels the complex or even removes H-NS from the DNA and thus abrogates repression by H-NS. The aim of the project is to analyze the interference of transcription and H-NS mediated repression qualitatively and quantitatively in vivo and in vitro, to elucidate a general mechanism which links the efficiency of repression by H-NS to the transcription rate.

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