RRC ID 48267
Author Okahashi N, Nakata M, Kuwata H, Kawabata S.
Title Streptococcus oralis Induces Lysosomal Impairment of Macrophages via Bacterial Hydrogen Peroxide.
Journal Infect Immun
Abstract Streptococcus oralis, an oral commensal, belongs to the mitis group of streptococci and occasionally causes opportunistic infections, such as bacterial endocarditis and bacteremia. Recently, we found that the hydrogen peroxide (H2O2) produced by S. oralis is sufficient to kill human monocytes and epithelial cells, implying that streptococcal H2O2 is a cytotoxin. In the present study, we investigated whether streptococcal H2O2 impacts lysosomes, organelles of the intracellular digestive system, in relation to cell death. S. oralis infection induced the death of RAW 264 macrophages in an H2O2-dependent manner, which was exemplified by the fact that exogenous H2O2 also induced cell death. Infection with either a mutant lacking spxB, which encodes pyruvate oxidase responsible for H2O2 production, or Streptococcus mutans, which does not produce H2O2, showed less cytotoxicity. Visualization of lysosomes with LysoTracker revealed lysosome deacidification after infection with S. oralis or exposure to H2O2, which was corroborated by acridine orange staining. Similarly, fluorescent labeling of lysosome-associated membrane protein-1 gradually disappeared during infection with S. oralis or exposure to H2O2 The deacidification and the following induction of cell death were inhibited by chelating iron in lysosomes. Moreover, fluorescent staining of cathepsin B indicated lysosomal destruction. However, treatment of infected cells with a specific inhibitor of cathepsin B had negligible effects on cell death; instead, it suppressed the detachment of dead cells from the culture plates. These results suggest that streptococcal H2O2 induces cell death with lysosomal destruction and then the released lysosomal cathepsins contribute to the detachment of the dead cells.
Volume 84(7)
Pages 2042-2050
Published 2016-7-1
DOI 10.1128/IAI.00134-16
PII IAI.00134-16
PMID 27113357
PMC PMC4936348
MeSH Animals Catalase / metabolism Cathepsin B / metabolism Cell Death / drug effects Cell Death / immunology Deferoxamine / pharmacology Hydrogen Peroxide / metabolism* Hydrogen-Ion Concentration Lysosomal-Associated Membrane Protein 1 / metabolism Lysosomes / metabolism* Macrophages / immunology* Macrophages / metabolism Macrophages / microbiology* Mice Models, Biological Streptococcal Infections / immunology Streptococcal Infections / microbiology Streptococcus oralis / physiology*
IF 3.201
Times Cited 6
General Microbes JCM 12997
Human and Animal Cells RAW 264(RCB0535)