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Infection and Immunity, January 2007, p. 83-90, Vol. 75, No. 1
0019-9567/07/$08.00+0     doi:10.1128/IAI.01475-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Capsule Enhances Pneumococcal Colonization by Limiting Mucus-Mediated Clearance{triangledown} ,{dagger}

Aaron L. Nelson,{ddagger} Aoife M. Roche,{ddagger} Jane M. Gould, Kannie Chim, Adam J. Ratner, and Jeffrey N. Weiser*

Departments of Microbiology and Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

Received 14 September 2006/ Returned for modification 14 October 2006/ Accepted 29 October 2006

Expression of a polysaccharide capsule is required for the full pathogenicity of many mucosal pathogens such as Streptococcus pneumoniae. Although capsule allows for evasion of opsonization and subsequent phagocytosis during invasive infection, its role during mucosal colonization, the organism's commensal state, remains unknown. Using a mouse model, we demonstrate that unencapsulated mutants remain capable of nasal colonization but at a reduced density and duration compared to those of their encapsulated parent strains. This deficit in colonization was not due to increased susceptibility to opsonophagocytic clearance involving complement, antibody, or the influx of Ly-6G-positive cells, including neutrophils seen during carriage. Rather, unencapsulated mutants remain agglutinated within lumenal mucus and, thus, are less likely to transit to the epithelial surface where stable colonization occurs. Studies of in vitro binding to immobilized human airway mucus confirmed the inhibitory effect of encapsulation. Likewise, pneumococcal variants expressing larger amounts of negatively charged capsule per cell were less likely to adhere to surfaces coated with human mucus and more likely to evade initial clearance in vivo. Removal of negatively charged sialic acid residues by pretreatment of mucus with neuraminidase diminished the antiadhesive effect of encapsulation. This suggests that the inhibitory effect of encapsulation on mucus binding may be mediated by electrostatic repulsion and offers an explanation for the predominance of anionic polysaccharides among the diverse array of unique capsule types. In conclusion, our findings demonstrate that capsule confers an advantage to mucosal pathogens distinct from its role in inhibition of opsonophagocytosis—escape from entrapment in lumenal mucus.

* Corresponding author. Mailing address: 402A Johnson Pavilion, Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104-6076. Phone: (215) 573-3511. Fax: (215) 898-9557. E-mail: weiser{at}mail.med.upenn.edu.

{triangledown} Published ahead of print on 6 November 2006.

Editor: A. Casadevall

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

{ddagger} A.L.N. and A.M.R. contributed equally to this study.

Infection and Immunity, January 2007, p. 83-90, Vol. 75, No. 1
0019-9567/07/$08.00+0     doi:10.1128/IAI.01475-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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