We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
The aryl hydrocarbon receptor and FOS mediate cytotoxicity induced by Acinetobacter baumannii.
- Authors
Kew, Chun; Prieto-Garcia, Cristian; Bhattacharya, Anshu; Tietgen, Manuela; MacNair, Craig R.; Carfrae, Lindsey A.; Mello-Vieira, João; Klatt, Stephan; Cheng, Yi-Lin; Rathore, Rajeshwari; Gradhand, Elise; Fleming, Ingrid; Tan, Man-Wah; Göttig, Stephan; Kempf, Volkhard A. J.; Dikic, Ivan
- 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. In this work, authors study the proteins in uninfected and Acinetobacter baumannii infected human cells to understand how this bacterium causes disease.
- Subjects
TRANSCRIPTION factors; ARYL hydrocarbon receptors; EXTRACELLULAR vesicles; FOS oncogenes; ACINETOBACTER baumannii
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-52118-7