http://hdl.handle.net/10033/76481 Tue, 21 May 2013 23:08:25 GMT 2013-05-21T23:08:25Z http://hdl.handle.net/10033/269743 Title: Thermosensing to adjust bacterial virulence in a fluctuating environment. Authors: Steinmann, Rebekka; Dersch, Petra Abstract: The lifecycle of most microbial pathogens can be divided into two states: existence outside and inside their hosts. The sudden temperature upshift experienced upon entry from environmental or vector reservoirs into a warm-blooded host is one of the most crucial signals informing the pathogens to adjust virulence gene expression and their host-stress survival program. This article reviews the plethora of sophisticated strategies that bacteria have evolved to sense temperature, and outlines the molecular signal transduction mechanisms used to modulate synthesis of crucial virulence determinants. The molecular details of thermal control through conformational changes of DNA, RNA and proteins are summarized, complex and diverse thermosensing principles are introduced and their potential as drug targets or synthetic tools are discussed. Tue, 01 Jan 2013 00:00:00 GMT http://hdl.handle.net/10033/269743 2013-01-01T00:00:00Z http://hdl.handle.net/10033/269594 Title: Crp Induces Switching of the CsrB and CsrC RNAs in Yersinia pseudotuberculosis and Links Nutritional Status to Virulence. Authors: Heroven, Ann Kathrin; Sest, Maike; Pisano, Fabio; Scheb-Wetzel, Matthias; Steinmann, Rebekka; Böhme, Katja; Klein, Johannes; Münch, Richard; Schomburg, Dietmar; Dersch, Petra Abstract: Colonization of the intestinal tract and dissemination into deeper tissues by the enteric pathogen Yersinia pseudotuberculosis demands expression of a special set of virulence factors important for the initiation and the persistence of the infection. In this study we demonstrate that many virulence-associated functions are coregulated with the carbohydrate metabolism. This link is mediated by the carbon storage regulator (Csr) system, including the regulatory RNAs CsrB and CsrC, and the cAMP receptor protein (Crp), which both control virulence gene expression in response to the nutrient composition of the medium. Here, we show that Crp regulates the synthesis of both Csr RNAs in an opposite manner. A loss of the crp gene resulted in a strong upregulation of CsrB synthesis, whereas CsrC levels were strongly reduced leading to downregulation of the virulence regulator RovA. Switching of the Csr RNA involves Crp-mediated repression of the response regulator UvrY which activates csrB transcription. To elucidate the regulatory links between virulence and carbon metabolism, we performed comparative metabolome, transcriptome, and phenotypic microarray analyses and found that Crp promotes oxidative catabolism of many different carbon sources, whereas fermentative patterns of metabolism are favored when crp is deleted. Mouse infection experiments further demonstrated that Crp is pivotal for a successful Y. pseudotuberculosis infection. In summary, placement of the Csr system and important virulence factors under control of Crp enables this pathogen to link its nutritional status to virulence in order to optimize biological fitness and infection efficiency through the infectious life cycle. Sun, 01 Jan 2012 00:00:00 GMT http://hdl.handle.net/10033/269594 2012-01-01T00:00:00Z http://hdl.handle.net/10033/264993 Title: Unique virulence properties of Yersinia enterocolitica O:3. Authors: Uliczka, Frank; Dersch, Petra Sun, 01 Jan 2012 00:00:00 GMT http://hdl.handle.net/10033/264993 2012-01-01T00:00:00Z http://hdl.handle.net/10033/252471 Title: Structural Basis for Intrinsic Thermosensing by the Master Virulence Regulator RovA of Yersinia. Authors: Quade, Nick; Mendonca, Chriselle; Herbst, Katharina; Heroven, Ann Kathrin; Ritter, Christiane; Heinz, Dirk W; Dersch, Petra Abstract: Pathogens often rely on thermosensing to adjust virulence gene expression. In yersiniae, important virulence-associated traits are under the control of the master regulator RovA, which uses a built-in thermosensor to control its activity. Thermal upshifts encountered upon host entry induce conformational changes in the RovA dimer that attenuate DNA binding and render the protein more susceptible to proteolysis. Here, we report the crystal structure of RovA in the free and DNA-bound forms and provide evidence that thermo-induced loss of RovA activity is promoted mainly by a thermosensing loop in the dimerization domain and residues in the adjacent C-terminal helix. These determinants allow partial unfolding of the regulator upon an upshift to 37 °C. This structural distortion is transmitted to the flexible DNA-binding domain of RovA. RovA contacts mainly the DNA backbone in a low-affinity binding mode, which allows the immediate release of RovA from its operator sites. We also show that SlyA, a close homolog of RovA from Salmonella with a very similar structure, is not a thermosensor and remains active and stable at 37 °C. Strikingly, changes in only three amino acids, reflecting evolutionary replacements in SlyA, result in a complete loss of the thermosensing properties of RovA and prevent degradation. In conclusion, only minor alterations can transform a thermotolerant regulator into a thermosensor that allows adjustment of virulence and fitness determinants to their thermal environment. Fri, 19 Oct 2012 00:00:00 GMT http://hdl.handle.net/10033/252471 2012-10-19T00:00:00Z