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Infection and Immunity, September 2008, p. 4079-4087, Vol. 76, No. 9
0019-9567/08/$08.00+0     doi:10.1128/IAI.01747-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Pneumolysin Released during Streptococcus pneumoniae Autolysis Is a Potent Activator of Intracellular Oxygen Radical Production in Neutrophils{triangledown}

Anna Martner,1* Claes Dahlgren,2 James C. Paton,3 and Agnes E. Wold1

Department of Clinical Bacteriology, Göteborg University, Guldhedsgatan 10A, 413 46 Göteborg, Sweden,1 Department of Rheumatology and Inflammatory Research, Göteborg University, Guldhedsgatan 10A, 413 46 Göteborg, Sweden,2 School of Molecular and Biomedical Science, University of Adelaide, Adelaide, S.A. 5005, Australia3

Received 30 December 2007/ Returned for modification 19 February 2008/ Accepted 8 June 2008

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.

* Corresponding author. Mailing address: Department of Clinical Bacteriology, Göteborg University, Guldhedsgatan 10A, 413 46 Göteborg, Sweden. Phone: 46 31 342 4623. Fax: 46 31 342 4975. E-mail: anna.martner{at}microbio.gu.se

{triangledown} Published ahead of print on 16 June 2008.

Editor: A. Camilli

Infection and Immunity, September 2008, p. 4079-4087, Vol. 76, No. 9
0019-9567/08/$08.00+0     doi:10.1128/IAI.01747-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Martner, A., Skovbjerg, S., Paton, J. C., Wold, A. E. (2009). Streptococcus pneumoniae Autolysis Prevents Phagocytosis and Production of Phagocyte-Activating Cytokines. Infect. Immun. 77: 3826-3837 [Abstract] [Full Text]  
  • Chattopadhyay, G., Chen, Q., Colino, J., Lees, A., Snapper, C. M. (2009). Intact Bacteria Inhibit the Induction of Humoral Immune Responses to Bacterial-Derived and Heterologous Soluble T Cell-Dependent Antigens. J. Immunol. 182: 2011-2019 [Abstract] [Full Text]  


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