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Infection and Immunity, September 2009, p. 3722-3730, Vol. 77, No. 9
0019-9567/09/$08.00+0 doi:10.1128/IAI.00228-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Department of Pediatrics and Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York,1 Department of Pediatrics and Microbiology, College of Physicians and Surgeons, Columbia University, New York, New York2
Received 26 February 2009/ Returned for modification 5 May 2009/ Accepted 23 June 2009
Streptococcus pneumoniae remains a major cause of bacteremia, pneumonia, and otitis media despite vaccines and effective antibiotics. The neuraminidase of S. pneumoniae, which catalyzes the release of terminal sialic acid residues from glycoconjugates, is involved in host colonization in animal models of infection and may provide a novel target for preventing pneumococcal infection. We demonstrate that the S. pneumoniae neuraminidase (NanA) cleaves sialic acid and show that it is involved in biofilm formation, suggesting an additional role in pathogenesis, and that it shares this property with the neuraminidase of Pseudomonas aeruginosa even though we show that the two enzymes are phylogenetically divergent. Using an in vitro model of biofilm formation incorporating human airway epithelial cells, we demonstrate that small-molecule inhibitors of NanA block biofilm formation and may provide a novel target for preventative therapy. This work highlights the role played by the neuraminidase in pathogenesis and represents an important step in drug development for prevention of colonization of the respiratory tract by this important pathogen.
Published ahead of print on 29 June 2009.
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