Analysis of Gene expression induced by anti-infective substances in pathogenic Staphylococci
PD Dr. Knut Ohlsen, Prof. Dr. Peter Jakob
Multiple resistant staphylococci that cause significant morbidity and mortality are the leading cause of nosocomial infections. Meanwhile, methicillin-resistant Staphylococcus aureus (MRSA) spread also in the community where highly virulent strains infect children and young adults that have no predisposing risk factors. Although some treatment options remain, the search for new antibacterial targets and lead compounds is urgently required to ensure that staphylococcal infections can be effectively treated in the future. Project part B5 aims at the search for new antiinfective substances against pathogenic staphylococci. Moreover, the mode of action of the new substances should be identified. DNA-microarray technique is applied to get gene expression patterns which allow the classification of a new substance into groups of antibiotics with known mode of action which are currently appliedin antimicrobial chemotherapy or into the group of substances targeting unknown structures. Along with DNA-microarray hybridization studies, proteomics, biochemical and genetical approaches will be applied to study the target structure of the new substances and to decipher the mode of action in detail. In addition, substances that inhibit the formation of biofilm of staphylococci should be identified. Moreover, different in vivo models are established to study the potency of new agents in vivo.
Selected, SFB-relevant Publications
T. Hertlein, V. Sturm, U. Lorenz, K. Sumathy, P. Jakob, K. Ohlsen; Bioluminescence and 19F magnetic resonance imaging visualize the efficacy of lysostaphin alone and in combination with oxacillin against Staphylococcus aureus in murine thigh and catheter-associated infection models. Antimicrob Agents Chemother 2013. doi:10.1128/AAC.01422-13
T. Hertlein, V. Sturm, P. Jakob, K. Ohlsen; (19)F Magnetic Resonance Imaging of Perfluorocarbons for the Evaluation of Response to Antibiotic Therapy in a Staphylococcus aureus Infection Model. PLoS One 2013, 8, e64440. doi:10.1371/journal.pone.0064440
N. Dunkel, T. Hertlein, R. Franz, O. Reuss, C. Sasse, T. Schäfer, K. Ohlsen, J. Morschhäuser; Role of different peptide transporters in nutrient acquisition in Candida albicans. Eukaryot Cell 2013. doi:10.1128/EC.00008-13
M. Tischer, G. Pradel, K. Ohlsen, U. Holzgrabe; Quaternary ammonium salts and their antimicrobial potential: targets or nonspecific interactions? ChemMedChem 2012, 7, 22-31.
V. J. Sturm, T. C. Basse-Lusebrink, T. Kampf, G. Stoll, P. M. Jakob; Improved encoding strategy for CPMG-based Bloch-Siegert B 1+ mapping. Magn Reson Med 2011.
T. M. Menzel, M. Tischer, P. Francois, J. Nickel, J. Schrenzel, H. Bruhn, A. Albrecht, L. Lehmann, U. Holzgrabe, K. Ohlsen; Mode-of-action studies of the novel bisquaternary bisnaphthalimide MT02 against Staphylococcus aureus. Antimicrob Agents Chemother 2011, 55, 311-320.
T. Hertlein, V. Sturm, S. Kircher, T. Basse-Lusebrink, D. Haddad, K. Ohlsen, P. Jakob; Visualization of abscess formation in a murine thigh infection model of Staphylococcus aureus by 19F-magnetic resonance imaging (MRI). PLoS One 2011, 6, e18246.
A. Cecil, C. Rikanovic, K. Ohlsen, C. Liang, J. Bernhardt, T. A. Oelschlaeger, T. Gulder, G. Bringmann, U. Holzgrabe, M. Unger, T. Dandekar; Modeling antibiotic and cytotoxic effects of the dimeric isoquinoline IQ-143 on metabolism and its regulation in Staphylococcus aureus, Staphylococcus epidermidis and human cells. Genome Biol 2011, 12, R24.
U. Lorenz, B. Lorenz, T. Schmitter, K. Streker, C. Erck, J. Wehland, J. Nickel, B. Zimmermann, K. Ohlsen; Functional antibodies targeting IsaA of Staphylococcus aureus augment host immune response and open new perspectives for antibacterial therapy. Antimicrob Agents Chemother 2010, Oct 18
U. Lorenz, T. Schäfer, K. Ohlsen, G.C. Tiurbe, C. Bühler, C.T. Germer, R. Kellersmann; In vivo detection of Staphylococcus aureus in biofilm on vascular prostheses using non-invasive biophotonic imaging. Eur J Vasc Surg 2010, Oct 11
T. Kampf, A. Fischer, T.C. Basse-Lüsebrink, G. Ladewig, F. Breuer, G. Stoll, P.M. Jakob, W.R. Bauer; Application of compressed sensing to in vivo 3D 19F CSI. J Magn Reson 2010, doi: 10.1016/j.jmr.2010.09.006
T.M. Menzel, M. Tischer, P. Francois, J. Nickel, J. Schrenzel, H. Bruhn, A. Albrecht, L. Lehmann, U. Holzgrabe, K. Ohlsen; Mode of action studies of the novel bisquaternary bisnaphthalimide MT02 against Staphylococcus aureus. Antimicrob Agents Chemother 2010, doi:10.1128/AAC.00586-10
M. Liebeke, H. Meyer, S. Donat, K. Ohlsen, M. Lalk; A metabolomic view of Staphylococcus aureus and ist Ser/Thr kinase and phosphatase deletion mutants: involvement in cell wall biosynthesis. Chem Biol 2010, 17, 820-830
M.J.T. Sibbald, T. Winter, M.M. van der Kooi-Pol, G. Buist, E. Tsompanidou, T. Bosma, T. Schäfer, K. Ohlsen, M. Hecker, H. Antelmann, S. Engelmann, J.M. van Dijl; Synthetic effects of secG and secY2 mutations on exoproteome biogenesis in Staphylococcus aureus. J Bacteriol 2010, 192, 3788-3800
S. Herbert, A.K. Ziebandt, K. Ohlsen, T. Schäfer, M. Hecker, D. Albrecht, R. Novick, F. Götz. Repair of global regulators in Staphylococcus aureus 8325 and comparative analysis with other clinical isolates. Infect. Immun. 2010, 78, 2877-2889
T. Geiger, C. Goerke, M. Fritz, T. Schäfer, K. Ohlsen, M. Liebeke, M. Lalk, C. Wolz. Role of the (p)ppGpp synthase RSH, a RelA/SpoT homolog, in stringent response and virulence of Staphylococcus aureus. Infect Immun 2010, 78, 1873-1883
Chlebowicz, M. A., K. Nganou, S. Kozytska, J.P. Arends, S. Engelmann, H. Grundmann, K. Ohlsen, J.M. van Dijl, G. Buist. Recombination between ccrC genes in a type VII SCCmec cassette of Staphylococcus aureus ST398 leads to MRSA - MSSA conversion in vivo. Antimicrob Agents Chemother 2010, 54, 783-791
L. Biswas, R. Biswas, C. Nerz, K. Ohlsen, M. Schlag, T. Schäfer, T. Lamkemeyer, A.K. Ziebandt, K. Hantke, R. Rosenstein, F. Götz; Role of the twin arginine translocation pathway in Staphylococcus. J Bacteriol 2010, 191, 5921-5929
S. Donat, K. Streker, T. Schirmeister, S. Rakette, T. Stehle, M. Liebeke, M. Lalk, K. Ohlsen; Transcriptome and functional analysis of the eukaryotic-type serine/threonine kinase pknB in Staphylococcus aureus. J Bacteriol 2009, 191, 4056-4069
B. Ramírez-Zavala, O. Reuß, Y.N. Park, K. Ohlsen, J. Morschhäuser; Environmental induction of white-opaque switching in Candida albicans. PLoS Pathog 2008, Jun 13;4(6):e1000089
U. Lorenz, C. Hüttinger, T. Schäfer, W. Ziebuhr, A. Thiede, J. Hacker, S. Engelmann, M. Hecker, K. Ohlsen; The alternative sigma factor sigma B of Staphylococcus aureus modulates virulence in experimental central venous catheter-related infections. Microbes Infect 2008, 10, 217-223
K. Streker, T. Schäfer, C. Freiberg, H. Brötz-Oesterhelt, J. Hacker, H. Labischinski, and K. Ohlsen; In vitro and in vivo validation of ligA and tarI as essential targets in Staphylococcus aureus. Antimicrob Agents Chemother 2008, 52, 4470-4474