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Infection and Immunity, August 2008, p. 3710-3716, Vol. 76, No. 8
0019-9567/08/$08.00+0     doi:10.1128/IAI.01748-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The Capsule Sensitizes Streptococcus pneumoniae to -Defensins Human Neutrophil Proteins 1 to 3

Katharina Beiter,^1,2, Florian Wartha,^1,2, Robert Hurwitz,³ Staffan Normark,^1,2 Arturo Zychlinsky,⁴ and Birgitta Henriques-Normark^1,2*

Department of Bacteriology, Swedish Institute for Infectious Disease Control, 171 82 Solna, Sweden,¹ Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden,² Biochemistry Core Facility, Max Planck Institute for Infection Biology, 10117 Berlin, Germany,³ Department of Cellular Microbiology, Max Planck Institute for Infection Biology, 10117 Berlin, Germany⁴

Received 31 December 2007/ Returned for modification 11 March 2008/ Accepted 1 May 2008

Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. Its polysaccharide capsule causes resistance to phagocytosis and interferes with the innate immune system's ability to clear infections at an early stage. Nevertheless, we found that encapsulated pneumococci are sensitive to killing by a human neutrophil granule extract. We fractionated the extract by high-performance liquid chromatography and identified -defensins by mass spectrometry as the proteins responsible for killing pneumococci. Analysis of sensitivity to the commercial -defensins human neutrophil proteins 1 to 3 (HNP1-3) confirmed these findings. We analyzed the sensitivities of different pneumococcal strains to HNP1-3 and found that encapsulated strains are efficiently killed at physiological concentrations (7.5 µg/ml). Surprisingly, nonencapsulated, nonvirulent pneumococci were significantly less sensitive to -defensins. The proposed mechanisms of -defensin resistance in nonencapsulated pneumococci is surface charge modification, e.g., by introduction of positive charge by D-alanylation of surface-exposed lipoteichoic acids. These mechanisms are surmounted by the presence of the capsule, which we hypothesize is masking these charge modifications. Hence, -defensins in the phagolysosome of neutrophils possibly contribute to intracellular killing after antibody-mediated opsonophagocytosis of encapsulated pneumococci.

Published ahead of print on 12 May 2008.

Editor: J. N. Weiser

These authors contributed equally to this work.

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