The NanA neuraminidase of Streptococcus pneumoniae is involved in biofilm formation.
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.
Parker
Dane
D
Department of Pediatrics and Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Soong
Grace
G
Planet
Paul
P
Brower
Jonathan
J
Ratner
Adam J
AJ
Prince
Alice
A
D001426:Bacterial Proteins / Q000502:physiology*; D018441:Biofilms / Q000254:growth & development*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D019158:N-Acetylneuraminic Acid / Q000494:pharmacology; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000502:physiology*; D010802:Phylogeny; D013296:Streptococcus pneumoniae / Q000201:enzymology / Q000502:physiology*
D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid