title: Pneumococcal Neuraminidase A (NanA) Promotes Biofilm Formation and Synergizes with Influenza A Virus in Nasal Colonization and Middle Ear Infection.
abstract: Even in the vaccine era,Streptococcus pneumoniae(the pneumococcus) remains a leading cause of otitis media, a significant public health burden, in large part because of the high prevalence of nasal colonization with the pneumococcus in children. The primary pneumococcal neuraminidase, NanA, which is a sialidase that catalyzes the cleavage of terminal sialic acids from host glycoconjugates, is involved in both of these processes. Coinfection with influenza A virus, which also expresses a neuraminidase, exacerbates nasal colonization and disease byS. pneumoniae, in part via the synergistic contributions of the viral neuraminidase. The specific role of its pneumococcal counterpart, NanA, in this interaction, however, is less well understood. We demonstrate in a mouse model that NanA-deficient pneumococci are impaired in their ability to cause both nasal colonization and middle ear infection. Coinfection with neuraminidase-expressing influenza virus andS. pneumoniaepotentiates both colonization and infection but not to wild-type levels, suggesting an intrinsic role of NanA. Usingin vitromodels, we show that while NanA contributes to both epithelial adherence and biofilm viability, its effect on the latter is actually independent of its sialidase activity. These data indicate that NanA contributes both enzymatically and nonenzymatically to pneumococcal pathogenesis and, as such, suggest that it is not a redundant bystander during coinfection with influenza A virus. Rather, its expression is required for the full synergism between these two pathogens.
authors.affiliation: Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Wren
authors.affiliation: Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Lance K
authors.initials: LK
authors.lastname: Blevins
authors.affiliation: Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Pang
authors.affiliation: Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.|Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Ankita
authors.initials: A
authors.lastname: Basu Roy
authors.affiliation: Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.|Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Melissa B
authors.initials: MB
authors.lastname: Oliver
authors.affiliation: Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Reimche
authors.affiliation: Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Jessie E
authors.initials: JE
authors.lastname: Wozniak
authors.affiliation: Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Martha A
authors.initials: MA
authors.lastname: Alexander-Miller
authors.affiliation: Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA swords@uab.edu.|Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: W Edward
authors.initials: WE
authors.lastname: Swords
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D018441:Biofilms; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005260:Female; D009980:Influenza A virus / Q000502:physiology*; D051379:Mice; D009297:Nasal Mucosa / Q000382:microbiology; D009439:Neuraminidase / Q000235:genetics / Q000378:metabolism*; D010033:Otitis Media / Q000382:microbiology* / Q000821:virology*; D013296:Streptococcus pneumoniae / Q000502:physiology*; D013559:Symbiosis
chemical_list: D009439:Neuraminidase
keywords: Streptococcus pneumoniae; biofilms; neuraminidase; otitis media