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Global analysis of the impact of linezolid onto virulence factor production in S. aureus USA300

Bonn, F., Pane-Farre, J., Schlueter, R., Schaffer, M., Fuchs, S., Bernhardt, J., Riedel, K., Otto, A., Voelker, U., van Dijl, J. M., Hecker, M., Maeder, U. & Becher, D., May-2016, In : International journal of medical microbiology. 306, 3, p. 131-140 10 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Florian Bonn
  • Jan Pane-Farre
  • Rabea Schlueter
  • Marc Schaffer
  • Stephan Fuchs
  • Joerg Bernhardt
  • Katharina Riedel
  • Andreas Otto
  • Uwe Voelker
  • Jan Maarten van Dijl
  • Michael Hecker
  • Ulrike Maeder
  • Doerte Becher

The translation inhibitor linezolid is an antibiotic of last resort against Gram-positive pathogens including methicillin resistant strains of the nosocomial pathogen Staphylococcus aureus. Linezolid is reported to inhibit production of extracellular virulence factors, but the molecular cause is unknown. To elucidate the physiological response of S. aureus to linezolid in general and the inhibition of virulence factor synthesis in particular a holistic study was performed.

Linezolid was added to exponentially growing S. aureus cells and the linezolid stress response was analyzed with transcriptomics and quantitative proteomics methods. In addition, scanning and transmission electron microscopy experiments as well as fluorescence microscopy analyses of the cellular DNA and membrane were performed.

As previously observed in studies on other translation inhibitors, S. aureus adapts its protein biosynthesis machinery to the reduced translation efficiency. For example the synthesis of ribosomal proteins was induced. Also unexpected results like a decline in the amount of extracellular and membrane proteins were obtained. In addition, cell shape and size changed after linezolid stress and cell division was diminished. Finally, the chromosome was condensed after linezolid stress and lost contact to the membrane. These morphological changes cannot be explained by established theories. A new hypothesis is discussed, which suggests that the reduced amount of membrane and extracellular proteins and observed defects in cell division are due to the disintegration of transertion complexes by linezolid. (C) 2016 Elsevier GmbH. All rights reserved.

Original languageEnglish
Pages (from-to)131-140
Number of pages10
JournalInternational journal of medical microbiology
Volume306
Issue number3
Publication statusPublished - May-2016

    Keywords

  • Mechanism of action, Transertion, Protein translocation, Cell division, Translation inhibition, RESISTANT STAPHYLOCOCCUS-AUREUS, SUBINHIBITORY CONCENTRATIONS, BACILLUS-SUBTILIS, PROTEIN-SYNTHESIS, FACTOR EXPRESSION, ESCHERICHIA-COLI, CELL-DIVISION, TRANSCRIPTIONAL RESPONSE, CHROMOSOME SEGREGATION, ANTIBIOTIC RESEARCH

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