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Berger-Bächi

Fakultäten » Medizinische Fakultät » Medizinische Mikrobiologie, Institut für » Prof. Dr. Brigitte Berger-Bächi » Berger-Bächi

Completed research project

Title / Titel Genetic and molecular basis of methicillin and glycopeptide resistance in Staphylococcus aureus
PDF Abstract (PDF, 14 KB)
Summary / Zusammenfassung Staphylococcus aureus possesses a wide range of virulence factors and has moreover the ability to adapt rapidly to antibiotic use by acquiring resistance. Methicillin resistant staphylococci (MRSA) are feared because they are resistant to all beta-lactam antibiotics and their derivatives. Recently MRSA isolates have emerged with decreased susceptibility to glycopeptides, the last antibiotic of choice against multiresistant MRSA. While methicillin resistance is based on the acqusisition of the mecA gene which codes for a novel, low-affinity penicillin-binding protein, glycopeptide resistance is due to selection of mutants during exposure to glycopeptides during therapy. The cell wall biosynthesis and composition plays an important role in resistance levels to both, beta-lactams and glycopeptides.
The studies proposed here apply to both classes of antibiotics, and may result in the identification of novel potential antibacterial targets. We will concentrate on two main topics:
a) Characterisation of peptidoglycan pentaglycine-interpeptide formation and analysis of the mode of action of the novel class of FemAB-like proteins which are involved in nonribosomal protein biosynthesis, and are regarded as lethal targets in S. aureus.
b) Characterisation of a novel, glycopeptide and ß-lactam-controlled regulator which influences methicillin and glycopeptide resistance. Functional analysis of an associated methionine sulfoxide reductase on S. aureus resistance and virulence.
Publications / Publikationen McCallum, N. Karauezuem, H., Getzmann, R., Bischoff, M. Majcherczyk, P., Berger-Bächi, B., Landmann, R. In vivo survival of teicoplanin-resistant Staphylococcus aureus and cost of teicoplanin resistance. Antimicrob Agents Chemother. 2006, 50:2352-2360

Schneider T., Senn M., Berger-Bächi B., Tossi A.,Sahl H-G., and Wiedemann, I. In vitro assembly of a complete, pentaglycine interpeptide bridge containing cell wall precursor (lipid II-Gly5) of Staphylococcus aureus. Molecular Microbiology 2004, 53:675-685

Rohrer, S., and Berger-Bächi B. FemABX peptidyltransferases: a link between branched chain cell wall peptide formation and beta-lactam resistance in Gram-positive cocci. Antimicrobial Agents and Chemotherapy 2003, 47:837-846

Keywords / Suchbegriffe Molecular Medicine, Medical Microbiology, Staphylococcus, resistance, methicillin, glycopeptide, cell wall biosynthesis, regulation
Project leadership and contacts /
Projektleitung und Kontakte
Prof. Dr. Brigitte Berger-Bächi (Project Leader) bberger@immv.uzh.ch
Funding source(s) /
Unterstützt durch
SNF (Personen- und Projektförderung)
Novartis Stiftung, Bonizzi-Theler Stiftung, Hartmann-Müller Stiftung
In collaboration with /
In Zusammenarbeit mit
Prof. H.-G. Sahl, Universität Bonn Germany

Dr. F. O'Brien, Curtin University, Perth

Australia

Prof. R. Landmann, University Hospital, Basel

Switzerland

Duration of Project / Projektdauer Nov 2004 to Oct 2007