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Type: Journal article
Title: Pneumolysin released during Streptococcus pneumoniae autolysis is a potent activator of intracellular oxygen radical production in neutrophils
Author: Martner, A.
Dahlgren, C.
Paton, J.
Wold, A.
Citation: Infection and Immunity, 2008; 76(9):4079-4087
Publisher: Amer Soc Microbiology
Issue Date: 2008
ISSN: 0019-9567
Statement of
Anna Martner, Claes Dahlgren, James C. Paton, and Agnes E. Wold
Abstract: Streptococcus pneumoniae is a major cause of otitis media, pneumonia, meningitis, and septicemia in humans. The host defense against this pathogen largely depends on bacterial killing by neutrophils. A peculiar property of pneumococci is their tendency to undergo autolysis, i.e., autoinduced disruption of the bacterial cell wall mediated by activation of the enzyme LytA, under stationary growth conditions. LytA is a virulence factor, but the molecular background for this has not been fully clarified. Here we examine how bacterial compounds released upon autolysis affect the production of reactive oxygen species (ROS) in neutrophils. We found that the S. pneumoniae strains A17 and D39 induced activation of the NADPH oxidase and the production of ROS in human neutrophils and that this activation was blocked when LytA was inactivated. The ROS-inducing bacterial substance released from autolyzed bacteria was identified as the cytoplasmic toxin pneumolysin. Further screening of clinical pneumococcal strains of various sero- and genotypes revealed that selected strains expressing toxins with reduced pneumolysin-dependent hemolytic activity had decreased abilities to induce ROS in neutrophils. Furthermore, a mutated form of purified pneumolysin lacking hemolytic and complement binding functions (PdT) did not induce any oxygen radical production. The ROS produced in response to pneumolysin formed mainly intracellularly, which may explain why this production was not detected previously. ROS released intracellularly may function as signaling molecules, modifying the function of neutrophils in bacterial defense.
Keywords: Neutrophils
Cells, Cultured
Streptococcus pneumoniae
Reactive Oxygen Species
Bacterial Proteins
Virulence Factors
Gene Deletion
Hemolysin Proteins
NADPH Oxidases
DOI: 10.1128/IAI.01747-07
Appears in Collections:Aurora harvest
Molecular and Biomedical Science publications

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