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Microbial human pathogens are constantly challenged by changing environmental conditions. They employ a number of regulatory mechanisms that impact metabolism and virulence to adapt to a given environment. We use the opportunistic human pathogen Pseudomonas aeruginosa as a model to study post-transcriptional regulation of virulence traits at the molecular level.
We employ state of the art methods in Microbiology, Genetics, Molecular Biology, Omics as well as Biophysical methods and Structural Biology to study the function of ribonucleoprotein complexes in post-transcriptional regulation.
1987: Dr. rer. nat. in Genetics, University of Munich
1987-1990: Postdoc at Texas A&M University, College Station and at the University of Colorado, Boulder, USA
1990: Group leader, Dept. of Microbiology and Genetics, University of Vienna
1996: Assoc. Prof., Dept. of Microbiology and Genetics, University of Vienna
2009: Prof. of Molecular Microbiology, University of Vienna
In P. aeruginosa the Sm-like protein Hfq contributes to post-transcriptional networks that control virulence traits including susceptibility to clinical relevant antibiotics. Hfq has been shown to exert these functions by assisting riboregulation by small regulatory RNAs, and by directly acting as a translational repressor on target mRNAs. Furthermore, Hfq has been recognized as the principle post-transcriptional regulator of catabolite repression in P. aeruginosa. It was shown to prevent ribosome loading on several mRNAs encoding catabolic enzymes. Moreover, the non-coding RNA CrcZ was shown to sequester Hfq, which in turn abrogates Hfq-mediated translational repression. This novel mechanistic twist on Hfq function not only highlighted the central role of RNA based regulation in P. aeruginosa carbon metabolism but also broadened the view of Hfq-mediated post-transcriptional mechanisms. In addition, cross-regulation by the RNA CrcZ, i.e. sequestration of Hfq, was shown to impact on antibiotic susceptibility. Thus, harnessing metabolic regulation may provide a means to (re)-sensitize P. aeruginosa to certain antimicrobials.
The carbon catabolite repression protein Crc is required for full translational repression of catabolic genes by Hfq. Extensive studies showed that Hfq forms a regulatory complex with Crc. Cryo-EM studies in collaboration with B. Luisi´s group in Cambridge revealed how Hfq cooperates with Crc to regulate translation, and provided a structural basis for an RNA code that guides global regulators to interact cooperatively and regulate different RNA targets.
Another research focus is directed towards a better understanding of post-transcriptional regulatory mechanisms in the crenarchaeon Sulfolobus solfataricus. Previous studies revealed the sequence of events in archaeal translation initiation as well as unprecedented function(s) of archaeal translation initiation factors. Our current studies concentrate on the elucidation of the function of archaeal SmAP proteins in S. solfataricus RNA turnover.
Architectural principles for Hfq/Crc-mediated regulation of gene expression.
Pei, Xue Yuan; Dendooven, Tom; Sonnleitner, Elisabeth; Chen, Shaoxia; Bläsi, Udo; Luisi, Ben F
Harnessing Metabolic Regulation to Increase Hfq-Dependent Antibiotic Susceptibility in Pseudomonas aeruginosa
Pusic, Petra; Sonnleitner, Elisabeth;Krennmayr, Beatrice; Heitzinger, Dorothea A.; Wolfinger, Michael T.; Resch, Armin; Bläsi, Udo
Interplay between the catabolite repression control protein Crc, Hfq and RNA in Hfq-dependent translational regulation in Pseudomonas aeruginosa.
Sonnleitner, Elisabeth; Wulf, Alexander; Campagne, Sébastien; Pei, Xue-Yuan; Wolfinger, Michael T; Forlani, Giada; Prindl, Konstantin; Abdou, Laetitia; Resch, Armin; Allain, Frederic H-T; Luisi, Ben F; Urlaub, Henning; Bläsi, Udo
Regulation of Hfq by the RNA CrcZ in Pseudomonas aeruginosa carbon catabolite repression.
Sonnleitner, Elisabeth; Bläsi, Udo
The Group Bläsi participates in the Doctoral Program "RNA Biology" funded by the Austrian Science Fund (FWF).
The Group Bläsi participates in the Special Research Program (SFB) "RNA-Reg - RNA regulation of the transcriptome" funded by the Austrian Science Fund (FWF). SFB's are peer-reviewed, highly interactive research networks, established to foster long-term, interdisciplinary collaboration of local research groups working on the frontiers of their thematic areas. In addition, the Bläsi group was supported by several stand alone grants from the FWF during the last decade.