title: Bacterial neuraminidase facilitates mucosal infection by participating in biofilm production.
abstract: Many respiratory pathogens, including Hemophilus influenzae, Streptococcus pneumoniae, and Pseudomonas aeruginosa, express neuraminidases that can cleave alpha2,3-linked sialic acids from glycoconjugates. As mucosal surfaces are heavily sialylated, neuraminidases have been thought to modify epithelial cells by exposing potential bacterial receptors. However, in contrast to neuraminidase produced by the influenza virus, a role for bacterial neuraminidase in pathogenesis has not yet been clearly established. We constructed a mutant of P. aeruginosa PAO1 by deleting the PA2794 neuraminidase locus (Delta2794) and tested its virulence and immunostimulatory capabilities in a mouse model of infection. Although fully virulent when introduced i.p., the Delta2794 mutant was unable to establish respiratory infection by i.n. inoculation. The inability to colonize the respiratory tract correlated with diminished production of biofilm, as assessed by scanning electron microscopy and in vitro assays. The importance of neuraminidase in biofilm production was further demonstrated by showing that viral neuraminidase inhibitors in clinical use blocked P. aeruginosa biofilm production in vitro as well. The P. aeruginosa neuraminidase has a key role in the initial stages of pulmonary infection by targeting bacterial glycoconjugates and contributing to the formation of biofilm. Inhibiting bacterial neuraminidases could provide a novel mechanism to prevent bacterial pneumonia.
authors.affiliation: Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Soong
authors.forename: Amanda
authors.initials: A
authors.lastname: Muir
authors.forename: Marisa I
authors.initials: MI
authors.lastname: Gomez
authors.forename: Jonathan
authors.initials: J
authors.lastname: Waks
authors.forename: Bharat
authors.initials: B
authors.lastname: Reddy
authors.forename: Paul
authors.initials: P
authors.lastname: Planet
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Singh
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Kanetko
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Wolfgang
authors.forename: Yu-Shan
authors.initials: YS
authors.lastname: Hsiao
authors.forename: Liang
authors.initials: L
authors.lastname: Tong
authors.forename: Alice
authors.initials: A
authors.lastname: Prince
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development*; D004195:Disease Models, Animal; D017353:Gene Deletion; D006193:Haemophilus influenzae / Q000201:enzymology* / Q000235:genetics; D007413:Intestinal Mucosa / Q000254:growth & development / Q000382:microbiology*; D051379:Mice; D008969:Molecular Sequence Data; D009439:Neuraminidase / Q000378:metabolism / Q000494:pharmacology*; D010587:Phagocytosis; D018410:Pneumonia, Bacterial / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000201:enzymology*
chemical_list: D001426:Bacterial Proteins; D009439:Neuraminidase