TY - JOUR
T1 - Dual role of hydrogen peroxide as an oxidant in pneumococcal pneumonia
AU - Mraheil, Mobarak Abu
AU - Flores Toque, Haroldo Alfredo
AU - La Pietra, Luigi
AU - Hamacher, Juerg
AU - Phanthok, Tenzing
AU - Verin, Alexander
AU - Gonzales, Joyce
AU - Su, Yunchao
AU - Fulton, David
AU - Eaton, Douglas C.
AU - Chakraborty, Trinad
AU - Lucas, Rudolf
N1 - Funding Information:
The study was funded by the National Institutes of Health HL134934 (Y.S.), HL125926 (D.F.), DK110409 (D.C.E.), and HL138410 (R.L.), by the Lungen-und Atmungsstiftung Bern, Switzerland ( J.H., R.L.), and by the German Research Foundation SFB-TR 84 ‘‘Innate Immunity of the Lung: Mechanisms of Pathogen Attack and Host Defense in Pneumonia’’ (M.A.M. and T.C.).
Publisher Copyright:
© Copyright 2021, Mary Ann Liebert, Inc., publishers 2021.
PY - 2021/4/20
Y1 - 2021/4/20
N2 - Significance: Streptococcus pneumoniae (Spn), a facultative anaerobic Gram-positive human pathogen with increasing rates of penicillin and macrolide resistance, is a major cause of lower respiratory tract infections worldwide. Pneumococci are a primary agent of severe pneumonia in children younger than 5 years and of community-acquired pneumonia in adults. A major defense mechanism toward Spn is the generation of reactive oxygen species, including hydrogen peroxide (H2O2), during the oxidative burst of neutrophils and macrophages. Paradoxically, Spn produces high endogenous levels of H2O2 as a strategy to promote colonization. Recent Advances: Pneumococci, which express neither catalase nor common regulators of peroxide stress resistance, have developed unique mechanisms to protect themselves from H2O2. Spn generates high levels of H2O2 as a strategy to promote colonization. Production of H2O2 moreover constitutes an important virulence phenotype and its cellular activities overlap and complement those of other virulence factors, such as pneumolysin, in modulating host immune responses and promoting organ injury. Critical Issues: This review examines the dual role of H2O2 in pneumococcal pneumonia, from the viewpoint of both the pathogen (defense mechanisms, lytic activity toward competing pathogens, and virulence) and the resulting host-response (inflammasome activation, endoplasmic reticulum stress, and damage to the alveolar-capillary barrier in the lungs). Future Directions: An understanding of the complexity of H2O2-mediated host-pathogen interactions is necessary to develop novel strategies that target these processes to enhance lung function during severe pneumonia.
AB - Significance: Streptococcus pneumoniae (Spn), a facultative anaerobic Gram-positive human pathogen with increasing rates of penicillin and macrolide resistance, is a major cause of lower respiratory tract infections worldwide. Pneumococci are a primary agent of severe pneumonia in children younger than 5 years and of community-acquired pneumonia in adults. A major defense mechanism toward Spn is the generation of reactive oxygen species, including hydrogen peroxide (H2O2), during the oxidative burst of neutrophils and macrophages. Paradoxically, Spn produces high endogenous levels of H2O2 as a strategy to promote colonization. Recent Advances: Pneumococci, which express neither catalase nor common regulators of peroxide stress resistance, have developed unique mechanisms to protect themselves from H2O2. Spn generates high levels of H2O2 as a strategy to promote colonization. Production of H2O2 moreover constitutes an important virulence phenotype and its cellular activities overlap and complement those of other virulence factors, such as pneumolysin, in modulating host immune responses and promoting organ injury. Critical Issues: This review examines the dual role of H2O2 in pneumococcal pneumonia, from the viewpoint of both the pathogen (defense mechanisms, lytic activity toward competing pathogens, and virulence) and the resulting host-response (inflammasome activation, endoplasmic reticulum stress, and damage to the alveolar-capillary barrier in the lungs). Future Directions: An understanding of the complexity of H2O2-mediated host-pathogen interactions is necessary to develop novel strategies that target these processes to enhance lung function during severe pneumonia.
KW - ARDS
KW - hydrogen peroxide
KW - pneumococci
KW - pneumonia
KW - pyruvate oxidase
KW - virulence factor
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U2 - 10.1089/ars.2019.7964
DO - 10.1089/ars.2019.7964
M3 - Review article
C2 - 32283950
AN - SCOPUS:85104051044
SN - 1523-0864
VL - 34
SP - 962
EP - 978
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
IS - 12
ER -