Bacterial neuraminidase facilitates mucosal infection by participating in biofilm production.
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.
Soong
Grace
G
Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Muir
Amanda
A
Gomez
Marisa I
MI
Waks
Jonathan
J
Reddy
Bharat
B
Planet
Paul
P
Singh
Pradeep K
PK
Kaneko
Yukihiro
Y
Kanetko
Yukihiro
Y
Wolfgang
Matthew C
MC
Hsiao
Yu-Shan
YS
Tong
Liang
L
Prince
Alice
A
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*
D001426:Bacterial Proteins; D009439:Neuraminidase