Two-component systems are widely distributed in prokaryotes where they control gene expression in response to diverse stimuli. To study the role of the sixteen putative two-component systems of Listeria monocytogenes systematically, in frame deletions were introduced into 15 out of the 16 response regulator genes and the resulting mutants were characterized. With one exception the deletion of the individual response regulator genes has only minor effects on in vitro and in vivo growth of the bacteria. The mutant carrying a deletion in the ortholog of the Bacillus subtilis response regulator gene degU showed a clearly reduced virulence in mice, indicating that DegU is involved in the regulation of virulence-associated genes.All free-living bacteria have the ability to respond and adapt rapidly to changes in their environment by coordinate changes in the expression of sets of genes. The signal transduction mechanisms allowing bacteria to modulate gene expression in response to diverse stimuli often involve two-component systems (TCSs), which are composed of a sensor kinase (HK) and a cognate response regulator (RR) (16). The sensor histidine kinase is composed of an N-terminal input domain which is frequently exposed to the periplasmic or extracellular space and a highly conserved cytoplasmic kinase domain which, in the presence of the appropriate stimulus, autophosphorylates at a highly conserved histidine residue. The phosphate group is subsequently transferred to an aspartic acid residue in the receiver domain of the cognate response regulator. Phosphorylation of the RR triggers a conformational change of the protein activating its output domain which frequently has DNA binding capability.Listeria monocytogenes, a facultative intracellular bacterial pathogen (43) is known to either live in the environment or to infect humans and other mammals, thereby encountering very different microenvironments. The expression of the listerial virulence genes is coordinately regulated to allow the bacteria to proceed through their intracellular life cycle. Central to virulence gene regulation is a protein called PrfA (25), which binds to palindromic DNA sequences in the upstream regions of most known virulence genes.So far, TCSs have not been studied comprehensively in L. monocytogenes. The availability of the complete genomic sequence of the L. monocytogenes strain EGD-e and the related apathogenic species Listeria innocua, allowed the in silico identification of 16 TCSs (15) in L. monocytogenes of which only one was absent in L. innocua.In order to study the role of the listerial TCSs for in vitro and in vivo survival and growth of L. monocytogenes more systematically, we constructed mutants with in-frame deletions in 15 out of the 16 response regulator genes. The characterization of the mutants demonstrated that only the deletion of the degU gene had a significant effect on the in vitro and in vivo growth of L. monocytogenes. Furthermore, we show that deletion of degU renders L. monocytogenes nonmotile due to the lack of f...

Chagas disease and its causative agent Trypanosoma cruzi are endemic in almost all countries in South and Middle America. Currently, there are more than 10 million affected people. It is the most common reason for heart failure and a frequent cause of intestinal problems in Latin America. The phenotype of the Chagas cardiomyopathy is varying. Dilative cardiomyopathy, often accompanied by an apical aneurysm is the most common finding in the end stage heart failure, but rhythm disorders like conduction blocks, ventricular or supraventricular forms of tachycardia or repolarization changes occur as well, mainly in the early stages. Migration of infected people leads to a distribution from the endemic countries to North America and Europe. Although more than 500,000 people of Latin American origin are currently living in Europe, Chagas disease is not considered as a public health problem, yet. Cases of transmission via blood donation, organ transplantation or from mother-to-child are reported for several European countries but there is no database for Germany. Current epidemiological data are mostly available from regional surveys from other countries or are extrapolated. Hence, there is a large variation in the estimated numbers on the incidence of Chagas. Robust and reliable data are lacking. This review gives an overview on the currently available data and calls for a German Chagas surveillance.

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The cell envelope stress response mediated by the LiaFSR Lm three-component system of Listeria monocytogenes is controlled via the phosphatase activity of the bifunctional histidine kinase LiaS Lm

Stimulation of IP3Rs with ET-1 induces Ca(2+ )release from the SR which is tunnelled to mitochondria via mitochondrial RyR leading to stimulation of mitochondrial ATP production.

An isogenic mutant of Listeria monocytogenes EGD with a deletion of the response regulator gene degU showed a lack of motility due to the absence of flagella. In the present study, we used two-dimensional gel electrophoresis, mass-spectrometry and microarray analyses to identify the listerial genes that depend on DegU for expression. We found that the two L. monocytogenes operons encoding flagella-specific genes and the monocistronically transcribed flaA gene are positively regulated by DegU at 24 degrees C, but are not expressed at 37 degrees C.

Background-We previously demonstrated that conditional overexpression of neuronal nitric oxide synthase (nNOS) inhibited L-type Ca 2ϩ channels and decreased myocardial contractility. However, nNOS has multiple targets within the cardiac myocyte. We now hypothesize that nNOS overexpression is cardioprotective after ischemia/reperfusion because of inhibition of mitochondrial function and a reduction in reactive oxygen species generation. Methods and Results-Ischemia/reperfusion injury in wild-type mice resulted in nNOS accumulation in the mitochondria.Similarly, transgenic nNOS overexpression caused nNOS abundance in mitochondria. nNOS translocation into the mitochondria was dependent on heat shock protein 90. Ischemia/reperfusion experiments in isolated hearts showed a cardioprotective effect of nNOS overexpression. Infarct size in vivo was also significantly reduced. nNOS overexpression also caused a significant increase in mitochondrial nitrite levels accompanied by a decrease of cytochrome c oxidase activity. Accordingly, O 2 consumption in isolated heart muscle strips was decreased in nNOS-overexpressing nNOS ϩ /␣MHC-tTA ϩ mice already under resting conditions. Additionally, we found that the reactive oxygen species concentration was significantly decreased in hearts of nNOS-overexpressing nNOS ϩ /␣MHC-tTA ϩ mice compared with noninduced nNOS ϩ /␣MHC-tTA ϩ animals. Conclusion-We demonstrated that conditional transgenic overexpression of nNOS resulted in myocardial protection after ischemia/reperfusion injury. Besides a reduction in reactive oxygen species generation, this might be caused by nitrite-mediated inhibition of mitochondrial function, which reduced myocardial oxygen consumption already under baseline conditions. (Circulation. 2010;122:1588-1603.)

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