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The aryl hydrocarbon receptor and FOS mediate cytotoxicity induced by Acinetobacter baumannii
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The aryl hydrocarbon receptor and FOS mediate cytotoxicity induced by Acinetobacter baumannii
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Journal Article
The aryl hydrocarbon receptor and FOS mediate cytotoxicity induced by Acinetobacter baumannii
2024
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/1
/ 13/106
/ 13/109
/ 13/89
/ 82/29
/ 82/58
/ 82/80
/ Acinetobacter baumannii - drug effects
/ Acinetobacter baumannii - genetics
/ Acinetobacter baumannii - metabolism
/ Acinetobacter Infections - metabolism
/ Acinetobacter Infections - microbiology
/ Animals
/ Bacteria
/ Basic Helix-Loop-Helix Transcription Factors - genetics
/ Basic Helix-Loop-Helix Transcription Factors - metabolism
/ Fos gene
/ Humanities and Social Sciences
/ Humans
/ Ligands
/ Mice
/ Proteins
/ Proto-Oncogene Proteins c-fos - genetics
/ Proto-Oncogene Proteins c-fos - metabolism
/ Receptors, Aryl Hydrocarbon - genetics
/ Receptors, Aryl Hydrocarbon - metabolism
/ Science
/ Toxicity
