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Hydrogen Peroxide Affects Growth of S. aureus Through Downregulation of Genes Involved in Pyrimidine Biosynthesis.
- Source :
-
Frontiers in immunology [Front Immunol] 2021 Sep 07; Vol. 12, pp. 673985. Date of Electronic Publication: 2021 Sep 07 (Print Publication: 2021). - Publication Year :
- 2021
-
Abstract
- Reactive oxygen species (ROS) play a crucial role in the cellular defense against S. aureus , as evidenced by the importance of this pathogen in patients lacking the ROS-generating phagocyte NADPH oxidase NOX2. ROS concentrations required to kill S. aureus in vitro are much higher than those found in the phagosome. We therefore hypothesized that sublethal ROS concentrations may play a role in S. aureus gene dysregulation and investigated the in vitro transcriptomic response of S. aureus to sublethal concentrations of hydrogen peroxide (H <subscript>2</subscript> O <subscript>2</subscript> ). A striking observation of these experiments was a coordinated and massive downregulation of genes involved in pyrimidine metabolism. Using transposon insertion mutants, we demonstrated that deletion of carA , a gene involved in pyrimidine synthesis, led to a significant growth defect and to an increased sensitivity of S. aureus to added H <subscript>2</subscript> O <subscript>2</subscript> . The phenotype of the carA mutant could be reversed through supplementation with the pyrimidine precursor uracil, or with a multicopy vector encoding carA . As opposed to the impact of ROS on extracellular survival, carA deletion did not affect the intracellular survival in neutrophils. Our results raise the possibility that ROS-dependent downregulation of pyrimidine metabolism might be a survival strategy of S. aureus , allowing colonization through intracellular survival, while decreasing the risk of killing the host through dampened extracellular growth.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2021 Buvelot, Roth, Jaquet, Lozkhin, Renzoni, Bonetti, Gaia, Laumay, Mollin, Stasia, Schrenzel, François and Krause.)
- Subjects :
- Bacterial Proteins metabolism
Cells, Cultured
Down-Regulation
Humans
Neutrophils microbiology
Reactive Oxygen Species metabolism
Gene Expression Regulation, Bacterial drug effects
Hydrogen Peroxide pharmacology
Pyrimidines metabolism
Staphylococcus aureus drug effects
Staphylococcus aureus metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 12
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 34557184
- Full Text :
- https://doi.org/10.3389/fimmu.2021.673985