@article{BeitzingerBronnhuberDuschaetal.2013,
  author    = {Beitzinger, Christoph and Bronnhuber, Annika and Duscha, Kerstin and Riedl, Zsuzsanna and Huber-Lang, Markus and Benz, Roland and Hajos, Gy{\"o}rgy and Barth, Holger},
  title     = {Designed Azolopyridinium Salts Block Protective Antigen Pores In Vitro and Protect Cells from Anthrax Toxin},
  series = {PLoS ONE},
  volume    = {8},
  journal   = {PLoS ONE},
  number    = {6},
  doi       = {10.1371/journal.pone.0066099},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130097},
  pages     = {e66099},
  year      = {2013},
  abstract  = {Background Several intracellular acting bacterial protein toxins of the AB-type, which are known to enter cells by endocytosis, are shown to produce channels. This holds true for protective antigen (PA), the binding component of the tripartite anthrax-toxin of Bacillus anthracis. Evidence has been presented that translocation of the enzymatic components of anthrax-toxin across the endosomal membrane of target cells and channel formation by the heptameric/octameric \(PA_{63}\) binding/translocation component are related phenomena. Chloroquine and some 4-aminoquinolones, known as potent drugs against Plasmodium falciparium infection of humans, block efficiently the \(PA_{63}\)-channel in a dose dependent way. Methodology/Principal Findings Here we demonstrate that related positively charged heterocyclic azolopyridinium salts block the \(PA_{63}\)-channel in the µM range, when both, inhibitor and \(PA_{63}\) are added to the same side of the membrane, the cis-side, which corresponds to the lumen of acidified endosomal vesicles of target cells. Noise-analysis allowed the study of the kinetics of the plug formation by the heterocycles. In vivo experiments using J774A.1 macrophages demonstrated that the inhibitors of \(PA_{63}\)-channel function also efficiently block intoxication of the cells by the combination lethal factor and \(PA_{63}\) in the same concentration range as they block the channels in vitro. Conclusions/Significance These results strongly argue in favor of a transport of lethal factor through the \(PA_{63}\)-channel and suggest that the heterocycles used in this study could represent attractive candidates for development of novel therapeutic strategies against anthrax.},
  language  = {en}
}
@article{GrausKonradBemmetal.2018,
  author    = {Graus, Dorothea and Konrad, Kai R. and Bemm, Felix and Nebioglu, Meliha G{\"o}rkem Patir and Lorey, Christian and Duscha, Kerstin and G{\"u}thoff, Tilman and Herrmann, Johannes and Ferjani, Ali and Cuin, Tracey Ann and Roelfsema, M. Rob G. and Schumacher, Karin and Neuhaus, H. Ekkehard and Marten, Irene and Hedrich, Rainer},
  title     = {High V-PPase activity is beneficial under high salt loads, but detrimental without salinity},
  series = {New Phytologist},
  volume    = {219},
  journal   = {New Phytologist},
  doi       = {10.1111/nph.15280},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227553},
  pages     = {1421-1432},
  year      = {2018},
  abstract  = {The membrane-bound proton-pumping pyrophosphatase (V-PPase), together with the V-type H+-ATPase, generates the proton motive force that drives vacuolar membrane solute transport. Transgenic plants constitutively overexpressing V-PPases were shown to have improved salinity tolerance, but the relative impact of increasing PPi hydrolysis and proton-pumping functions has yet to be dissected. For a better understanding of the molecular processes underlying V-PPase-dependent salt tolerance, we transiently overexpressed the pyrophosphate-driven proton pump (NbVHP) in Nicotiana benthamiana leaves and studied its functional properties in relation to salt treatment by primarily using patch-clamp, impalement electrodes and pH imaging. NbVHP overexpression led to higher vacuolar proton currents and vacuolar acidification. After 3 d in salt-untreated conditions, V-PPase-overexpressing leaves showed a drop in photosynthetic capacity, plasma membrane depolarization and eventual leaf necrosis. Salt, however, rescued NbVHP-hyperactive cells from cell death. Furthermore, a salt-induced rise in V-PPase but not of V-ATPase pump currents was detected in nontransformed plants. The results indicate that under normal growth conditions, plants need to regulate the V-PPase pump activity to avoid hyperactivity and its negative feedback on cell viability. Nonetheless, V-PPase proton pump function becomes increasingly important under salt stress for generating the pH gradient necessary for vacuolar proton-coupled Na+ sequestration.},
  language  = {en}
}