Effect of intranasal inoculation of Streptococcus pneumoniae on the structure of the surface carbohydrates of the chinchilla eustachian tube and middle ear mucosa

Linder, Thomas; Daniels, Robert L.; Lim, David J.; DeMaria, Thomas F.

doi:10.1006/mpat.1994.1043

Cited by 42 publications

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“…Moreover, S. pneumoniae neuraminidase has been detected in 78% of culture-positive middle ear effusions from patients with acute OM and in 96% of S. pneumoniaepositive middle ear effusions from patients with chronic OM (4). Two recent reports from our laboratory indicate that during S. pneumoniae-induced OM in the chinchilla model, terminal sialic acid residues are removed from the epithelial surface lining the lumen of the eustachian tube, presumably as a result of S. pneumoniae neuraminidase production (7,8). Similar data have been derived clinically from adenoidal tissue obtained from children with chronic OM with effusion.…”

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confidence: 85%

“…S. pneumoniae neuraminidase may affect middle ear pressure by disrupting the eustachian tube function, a key determinant in the maintenance of normal middle ear pressure. Previous data from our laboratory indicate that sialic acid residues are removed from the eustachian tube during S. pneumoniae OM in the chinchilla (7,8). The extent of this disruption of the carbohydrate surface structure and the surfactant-like substances known to be required for normal eustachian tube function has not been elucidated.…”

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confidence: 93%

“…Although a precise role for S. pneumoniae neuraminidase in the pathogenesis of S. pneumoniae-caused diseases has not been established, it has been proposed that neuraminidase could enhance colonization by decreasing the viscosity of mucus (13) or by exposing cell surface receptors for S. pneumoniae (1,7,8). All clinical S. pneumoniae isolates examined to date have been shown to produce neuraminidase (6).…”

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confidence: 99%

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Evaluation of the Virulence of a Streptococcus pneumoniae Neuraminidase-Deficient Mutant in Nasopharyngeal Colonization and Development of Otitis Media in the Chinchilla Model

et al. 2000

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Considerable evidence has implicated Streptococcus pneumoniae neuraminidase in the pathogenesis of otitis media (OM); however, its exact role has not been conclusively established. Recently, an S. pneumoniae neuraminidase-deficient mutant, ⌬NA1, has been constructed by insertion-duplication mutagenesis of the nanA gene of S. pneumoniae strain D39. The relative ability of ⌬NA1 and the D39 parent strain to colonize the nasopharynx and to induce OM subsequent to intranasal inoculation and to survive in the middle ear cleft after direct challenge of the middle ear were evaluated in the chinchilla model. Nasopharyngeal colonization data indicate a significant difference in the ability of the ⌬NA1 mutant to colonize as well as to persist in the nasopharynx. The neuraminidase-deficient mutant was eliminated from the nasopharynx 2 weeks earlier than the D39 parent strain. Both the parent and the mutant exhibited similar virulence levels and kinetics during the first week after direct inoculation of the middle ear. The ⌬NA1 neuraminidase-deficient mutant, however, was then completely eliminated from the middle ear by day 10 postchallenge, 11 days before the D39 parent strain. Data from this study indicate that products of the nanA gene have an impact on the ability of S. pneumoniae to colonize and persist in the nasopharynx as well as the middle ear.Streptococcus pneumoniae is one of the primary bacterial pathogens associated with otitis media (OM) and accounts for approximately 30% of all cases of this disease (11).Neuraminidase is an enzyme which cleaves N-acetylneuraminic acid from mucin, glycolipids, glycoproteins, and oligosaccharides on host cell surfaces. Although a precise role for S. pneumoniae neuraminidase in the pathogenesis of S. pneumoniae-caused diseases has not been established, it has been proposed that neuraminidase could enhance colonization by decreasing the viscosity of mucus (13) or by exposing cell surface receptors for S. pneumoniae (1,7,8). All clinical S. pneumoniae isolates examined to date have been shown to produce neuraminidase (6). Production of neuraminidase is believed to contribute to the poor prognosis for pneumococcal meningitis (12). Moreover, S. pneumoniae neuraminidase has been detected in 78% of culture-positive middle ear effusions from patients with acute OM and in 96% of S. pneumoniaepositive middle ear effusions from patients with chronic OM (4). Two recent reports from our laboratory indicate that during S. pneumoniae-induced OM in the chinchilla model, terminal sialic acid residues are removed from the epithelial surface lining the lumen of the eustachian tube, presumably as a result of S. pneumoniae neuraminidase production (7, 8). Similar data have been derived clinically from adenoidal tissue obtained from children with chronic OM with effusion. Adenoids colonized with S. pneumoniae demonstrated removal of sialic acid and exposure of N-acetylglycosamine (9). The result is exposure of GlcNAc␤1-4Gal, which is part of one of the eukaryotic receptors of S. pneumoniae (1). More...

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confidence: 85%

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confidence: 93%

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confidence: 99%

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Evaluation of the Virulence of a Streptococcus pneumoniae Neuraminidase-Deficient Mutant in Nasopharyngeal Colonization and Development of Otitis Media in the Chinchilla Model

et al. 2000

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“…Production of NanA can be detected in vivo, and its expression is upregulated upon interaction with host cells (27,39,46,58). The pneumococcal neuraminidase modifies host glycoconjugates, including immune defense proteins (22,23), and exposes potential binding receptors (3,26,28,54,55). Pneumococcal neuraminidase activity also provides a source of carbohydrates for bacterial metabolism, cleaving sugars from the mucosal surface (8,23,61), but whether this significantly contributes to bacterial growth in vivo has not been clearly established.…”

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The NanA Neuraminidase of Streptococcus pneumoniae Is Involved in Biofilm Formation

et al. 2009

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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.

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“…Neuraminidase is an enzyme that cleaves N-acetylneuraminic acid from mucin, glycolipids, glycoproteins, and oligosaccharides on host cell surfaces (18,20). Results of studies conducted in our laboratory indicate that during S. pneumoniae-induced OM in the chinchilla, terminal sialic acid residues are removed from the surface of the epithelium lining the lumen of the eustachian tube, presumably by neuraminidase, resulting in the exposure of GlcNAc ␤ 1-4 Gal, which is part of one of the S. pneumoniae eukaryotic receptors (10,11). Additional studies conducted by our laboratory implicate neuraminidase as a virulence factor for S. pneumoniae (23,24).…”

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Immunization with Native or Recombinant Streptococcus pneumoniae Neuraminidase Affords Protection in the Chinchilla Otitis Media Model

2004

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Streptococcus pneumoniae neuraminidase has been implicated as a virulence factor in the pathogenesis of pneumococcal otitis media. In this study, native neuraminidase was partially purified from cultures of S. pneumoniae by serial chromatography with DEAE-Sepharose and Sephacryl S-200. Recombinant neuraminidase, a 3,038-bp fragment of the neuraminidase A (nanA) gene, was cloned into the pET-28b vector and then expressed at high levels in Escherichia coli. Chinchillas were immunized subcutaneously with either the gel-purified native or recombinant neuraminidase, and all responded with elevated titers of antineuraminidase antibody in serum. Immunization with neuraminidase resulted in a significant reduction in nasopharyngeal colonization as well as in the incidence of otitis media with effusion. These data demonstrate for the first time that neuraminidase affords protection against S. pneumoniae nasopharyngeal colonization and experimental otitis media.Streptococcus pneumoniae is the most frequent cause of otitis media (OM) in children, accounting for 30% of the cases of acute OM and 5% of the cases of chronic OM with effusion (OME) (14). All S. pneumoniae isolates to date have been shown to produce neuraminidase (9). S. pneumoniae neuraminidase has been detected in 78% of culture-positive human middle ear effusions from patients with acute OM and in 96% of S. pneumoniae-positive middle ear effusions from patients with chronic OME (7). Neuraminidase is an enzyme that cleaves N-acetylneuraminic acid from mucin, glycolipids, glycoproteins, and oligosaccharides on host cell surfaces (18,20). Results of studies conducted in our laboratory indicate that during S. pneumoniae-induced OM in the chinchilla, terminal sialic acid residues are removed from the surface of the epithelium lining the lumen of the eustachian tube, presumably by neuraminidase, resulting in the exposure of GlcNAc ␤ 1-4 Gal, which is part of one of the S. pneumoniae eukaryotic receptors (10, 11). Additional studies conducted by our laboratory implicate neuraminidase as a virulence factor for S. pneumoniae (23,24). We found that the ability of a neuraminidase-deficient mutant to colonize and persist within the nasopharynx and middle ear was significantly impaired relative to the parent strain (21). These data indicate that neuraminidase plays an important role in the ability of S. pneumoniae to colonize and persist in the nasopharynx and induce OM. For this reason, we have chosen to investigate whether neuraminidase is a protective antigen and a potential protein-based vaccine candidate in the prevention of S. pneumoniae nasopharyngeal (NP) colonization and OM.Purification of native neuraminidase. Neuraminidase was purified from whole-cell lysates as previously described by Lock et al. (12). S. pneumoniae 6A (EF3114) was used for purification of native neuraminidase as well as intranasal inoculation in the chinchilla model of OM and has been described in detail previously (1,22). Fractions from a DEAESepharose column containing neuraminidase (identifi...

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Effect of intranasal inoculation of Streptococcus pneumoniae on the structure of the surface carbohydrates of the chinchilla eustachian tube and middle ear mucosa

Cited by 42 publications

References 0 publications

Evaluation of the Virulence of a Streptococcus pneumoniae Neuraminidase-Deficient Mutant in Nasopharyngeal Colonization and Development of Otitis Media in the Chinchilla Model

Evaluation of the Virulence of a Streptococcus pneumoniae Neuraminidase-Deficient Mutant in Nasopharyngeal Colonization and Development of Otitis Media in the Chinchilla Model

The NanA Neuraminidase of Streptococcus pneumoniae Is Involved in Biofilm Formation

Immunization with Native or Recombinant Streptococcus pneumoniae Neuraminidase Affords Protection in the Chinchilla Otitis Media Model

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