Oxidation of hemoproteins by Streptococcus pneumoniae collapses the cell cytoskeleton and disrupts mitochondrial respiration leading to the cytotoxicity of human lung cells.

Autor:	Scasny A; Department of Cell and Molecular Biology, School of Medicine, University of Mississippi Medical Center , Jackson, Mississippi, USA.; Center for Immunology and Microbial Research, School of Medicine, University of Mississippi Medical Center , Jackson, Mississippi, USA., Alibayov B; Department of Cell and Molecular Biology, School of Medicine, University of Mississippi Medical Center , Jackson, Mississippi, USA.; Center for Immunology and Microbial Research, School of Medicine, University of Mississippi Medical Center , Jackson, Mississippi, USA., Khan F; Department of Cell and Molecular Biology, School of Medicine, University of Mississippi Medical Center , Jackson, Mississippi, USA.; Center for Immunology and Microbial Research, School of Medicine, University of Mississippi Medical Center , Jackson, Mississippi, USA., Rao SJ; Department of Otolaryngology-Head and Neck Surgery, The Ohio State School of Medicine, The Ohio State Wexner Medical Center , Columbus, Ohio, USA., Murin L; Department of Cell and Molecular Biology, School of Medicine, University of Mississippi Medical Center , Jackson, Mississippi, USA.; Center for Immunology and Microbial Research, School of Medicine, University of Mississippi Medical Center , Jackson, Mississippi, USA., Jop Vidal AG; Department of Cell and Molecular Biology, School of Medicine, University of Mississippi Medical Center , Jackson, Mississippi, USA.; Center for Immunology and Microbial Research, School of Medicine, University of Mississippi Medical Center , Jackson, Mississippi, USA., Smith P; Mississippi INBRE Research Scholar, University of Southern Mississippi , Jackson, Mississippi, USA., Li W; Department of Physics, Emory University , Atlanta, Georgia, USA., Edwards K; Department of Cell and Molecular Biology, School of Medicine, University of Mississippi Medical Center , Jackson, Mississippi, USA., Warncke K; Department of Physics, Emory University , Atlanta, Georgia, USA., Vidal JE; Department of Cell and Molecular Biology, School of Medicine, University of Mississippi Medical Center , Jackson, Mississippi, USA.; Center for Immunology and Microbial Research, School of Medicine, University of Mississippi Medical Center , Jackson, Mississippi, USA.
Jazyk:	angličtina
Zdroj:	Microbiology spectrum [Microbiol Spectr] 2024 Jan 11; Vol. 12 (1), pp. e0291223. Date of Electronic Publication: 2023 Dec 12.
DOI:	10.1128/spectrum.02912-23
Abstrakt:	Importance: Streptococcus pneumoniae (Spn) colonizes the lungs, killing millions every year. During its metabolism, Spn produces abundant amounts of hydrogen peroxide. When produced in the lung parenchyma, Spn-hydrogen peroxide (H 2 O 2 ) causes the death of lung cells, and details of the mechanism are studied here. We found that Spn-H 2 O 2 targets intracellular proteins, resulting in the contraction of the cell cytoskeleton and disruption of mitochondrial function, ultimately contributing to cell death. Intracellular proteins targeted by Spn-H 2 O 2 included cytochrome c and, surprisingly, a protein of the cell cytoskeleton, beta-tubulin. To study the details of oxidative reactions, we used, as a surrogate model, the oxidation of another hemoprotein, hemoglobin. Using the surrogate model, we specifically identified a highly reactive radical whose creation was catalyzed by Spn-H 2 O 2 . In sum, we demonstrated that the oxidation of intracellular targets by Spn-H 2 O 2 plays an important role in the cytotoxicity caused by Spn, thus providing new targets for interventions. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu