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An Aromatic Hydroxyamide Attenuates Multiresistant Staphylococcus aureus Toxin Expression

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2016

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Vomacka, Jan
Korotkov, Vadim S.
Bauer, Bianca
Weinandy, Franziska
Kunzmann, Martin H.
Krysiak, Joanna
Baron, Oliver
Lorenz-Baath, Katrin
Sieber, Stephan A.

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https://doi.org/10.1002/chem.201503981
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Chemistry - A European Journal. 2016, 22(5), pp. 1622-1630. ISSN 0947-6539. eISSN 1521-3765. Available under: doi: 10.1002/chem.201503981

Zusammenfassung

Methicillin-resistant Staphylococcus aureus (MRSA) causes severe infections with only few effective antibiotic therapies currently available. To approach this challenge, chemical entities with a novel and resistance-free mode of action are desperately needed. Here, we introduce a new hydroxyamide compound that effectively reduces the expression of devastating toxins in various S. aureus and MRSA strains. The molecular mechanism was investigated by transcriptome analysis as well as by affinity-based protein profiling. Down-regulation of several pathogenesis associated genes suggested the inhibition of a central virulence-related pathway. Mass spectrometry-based chemical proteomics revealed putative molecular targets. Systemic treatment with the hydroxyamide showed significant reduction of abscess sizes in a MRSA mouse skin infection model. The absence of resistance development in vitro further underlines the finding that targeting virulence could lead to prolonged therapeutic options in comparison to antibiotics that directly address bacterial survival.

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ISO 690VOMACKA, Jan, Vadim S. KOROTKOV, Bianca BAUER, Franziska WEINANDY, Martin H. KUNZMANN, Joanna KRYSIAK, Oliver BARON, Thomas BÖTTCHER, Katrin LORENZ-BAATH, Stephan A. SIEBER, 2016. An Aromatic Hydroxyamide Attenuates Multiresistant Staphylococcus aureus Toxin Expression. In: Chemistry - A European Journal. 2016, 22(5), pp. 1622-1630. ISSN 0947-6539. eISSN 1521-3765. Available under: doi: 10.1002/chem.201503981
BibTex
@article{Vomacka2016Aroma-33631,
  year={2016},
  doi={10.1002/chem.201503981},
  title={An Aromatic Hydroxyamide Attenuates Multiresistant Staphylococcus aureus Toxin Expression},
  number={5},
  volume={22},
  issn={0947-6539},
  journal={Chemistry - A European Journal},
  pages={1622--1630},
  author={Vomacka, Jan and Korotkov, Vadim S. and Bauer, Bianca and Weinandy, Franziska and Kunzmann, Martin H. and Krysiak, Joanna and Baron, Oliver and Böttcher, Thomas and Lorenz-Baath, Katrin and Sieber, Stephan A.}
}
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