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The aryl hydrocarbon receptor and FOS mediate cytotoxicity induced by Acinetobacter baumannii

Author

Listed:
  • Chun Kew

    (Goethe University
    Goethe University)

  • Cristian Prieto-Garcia

    (Goethe University)

  • Anshu Bhattacharya

    (Goethe University
    Goethe University)

  • Manuela Tietgen

    (Hospital of the Goethe University
    University Center of Competence for Infection Control of the State of Hesse)

  • Craig R. MacNair

    (1 DNA Way)

  • Lindsey A. Carfrae

    (1 DNA Way)

  • João Mello-Vieira

    (Goethe University
    Goethe University)

  • Stephan Klatt

    (Goethe University)

  • Yi-Lin Cheng

    (Goethe University
    Goethe University
    National Cheng Kung University)

  • Rajeshwari Rathore

    (Goethe University)

  • Elise Gradhand

    (Goethe University)

  • Ingrid Fleming

    (Goethe University)

  • Man-Wah Tan

    (1 DNA Way)

  • Stephan Göttig

    (Hospital of the Goethe University)

  • Volkhard A. J. Kempf

    (Hospital of the Goethe University)

  • Ivan Dikic

    (Goethe University
    Goethe University
    Branch Translational Medicine and Pharmacology
    Max Planck Institute of Biophysics)

Abstract

Acinetobacter baumannii is a pathogenic and multidrug-resistant Gram-negative bacterium that causes severe nosocomial infections. To better understand the mechanism of pathogenesis, we compare the proteomes of uninfected and infected human cells, revealing that transcription factor FOS is the host protein most strongly induced by A. baumannii infection. Pharmacological inhibition of FOS reduces the cytotoxicity of A. baumannii in cell-based models, and similar results are also observed in a mouse infection model. A. baumannii outer membrane vesicles (OMVs) are shown to activate the aryl hydrocarbon receptor (AHR) of host cells by inducing the host enzyme tryptophan-2,3-dioxygenase (TDO), producing the ligand kynurenine, which binds AHR. Following ligand binding, AHR is a direct transcriptional activator of the FOS gene. We propose that A. baumannii infection impacts the host tryptophan metabolism and promotes AHR- and FOS-mediated cytotoxicity of infected cells.

Suggested Citation

  • Chun Kew & Cristian Prieto-Garcia & Anshu Bhattacharya & Manuela Tietgen & Craig R. MacNair & Lindsey A. Carfrae & João Mello-Vieira & Stephan Klatt & Yi-Lin Cheng & Rajeshwari Rathore & Elise Gradhan, 2024. "The aryl hydrocarbon receptor and FOS mediate cytotoxicity induced by Acinetobacter baumannii," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52118-7
    DOI: 10.1038/s41467-024-52118-7
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    References listed on IDEAS

    as
    1. Jianjin Shi & Yue Zhao & Yupeng Wang & Wenqing Gao & Jingjin Ding & Peng Li & Liyan Hu & Feng Shao, 2014. "Inflammatory caspases are innate immune receptors for intracellular LPS," Nature, Nature, vol. 514(7521), pages 187-192, October.
    2. Alban Bessede & Marco Gargaro & Maria T. Pallotta & Davide Matino & Giuseppe Servillo & Cinzia Brunacci & Silvio Bicciato & Emilia M. C. Mazza & Antonio Macchiarulo & Carmine Vacca & Rossana Iannitti , 2014. "Aryl hydrocarbon receptor control of a disease tolerance defence pathway," Nature, Nature, vol. 511(7508), pages 184-190, July.
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