Immunization with Recombinant
            <i>Streptococcus pneumoniae</i>
            Neuraminidase NanA Protects Chinchillas against Nasopharyngeal Colonization

Tong, Hua Hua; Li, D.; Chen, S.; Long, James P.; DeMaria, Thomas F.

doi:10.1128/iai.73.11.7775-7778.2005

Cited by 33 publications

(28 citation statements)

References 32 publications

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“…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. Several studies have suggested that nanA mutants colonize the rodent respiratory tract less efficiently than wild-type strains (31,40,52), and vaccination with purified NanA affords some protection against nasopharyngeal colonization and otitis media (29,30,53). However, the differences can be mouse strain and animal model dependent (6,13,22,23).…”

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confidence: 87%

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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confidence: 87%

The NanA Neuraminidase of Streptococcus pneumoniae Is Involved in Biofilm Formation

et al. 2009

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“…The sialic acid residues contribute to a range of important biological functions, including cellular interactions and stabilizing the conformation of glycoproteins and cellular membranes; these residues also expose or mask receptors for ligands, antibodies, or enzymes and contribute to the function and stability of glycoproteins in serum (3,40). Sialidases are implicated in the pathogenicity of some bacteria, including Clostridium perfringens (33), Streptococcus pneumoniae (46), Pasteurella multocida (42), and Pseudomonas aeruginosa (41). They can modify the host's ability to respond to bacterial infection by increasing the susceptibility of immunoglobulin molecules to proteolytic degradation (28).…”

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confidence: 99%

An Orthologue of Bacteroides fragilis NanH Is the Principal Sialidase in Tannerella forsythia

Thompson¹,

Homer²,

Rao³

et al. 2009

J Bacteriol

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Sialidase activity is a putative virulence factor of the anaerobic periodontal pathogen Tannerella forsythia, but it is uncertain which genes encode this activity. Characterization of a putative sialidase, SiaHI, by others, indicated that this protein alone may not be responsible for all of the sialidase activity. We describe a second sialidase in T. forsythia (TF0035), an orthologue of Bacteroides fragilis NanH, and its expression in Escherichia coli. Sialidase activity of the expressed NanH was confirmed by using 2-(4-methylumbelliferyl)-␣-D-N-acetylneuraminic acid as a substrate. Biochemical characterization of the recombinant T. forsythia NanH indicated that it was active over a broad pH range, with optimum activity at pH 5.5. This enzyme has high affinity for 2-(4-methylumbelliferyl)-␣-D-N-acetylneuraminic acid (K m of 32.9 ؎ 10.3 M) and rapidly releases 4-methylumbelliferone (V max of 170.8 ؎ 11.8 nmol of 4-methylumbelliferone min ؊1 mg of protein ؊1 ). E. coli lysates containing recombinant T. forsythia NanH cleave sialic acid from a range of substrates, with a preference for ␣2-3 glycosidic linkages. The genes adjacent to nanH encode proteins apparently involved in the metabolism of sialic acid, indicating that the NanH sialidase is likely to be involved in nutrient acquisition.

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“…Among these are the pneumolysin toxoid (32), pneumococcal surface protein A (PspA) (5), neuraminidase (NanA) (38), pneumococcal histidine triad proteins A, B, and D (PhtA, PhtB, and PhtD) (1), and pneumococcal surface adhesion molecule A (PsaA) (35). Inclusion of a combination of two or more antigens will most likely be necessary to confer broad protection against the highly heterogeneous pneumococcal population (31).…”

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confidence: 99%

Live Attenuated Streptococcus pneumoniae Strains Induce Serotype-Independent Mucosal and Systemic Protection in Mice

Roche¹,

King²,

Weiser

2007

Infect Immun

118

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Streptococcus pneumoniae is an important human pathogen causing both mucosal (otitis media and pneumonia) and systemic (sepsis and meningitis) diseases. Due to increasing rates of antibiotic resistance, there is an urgent need to improve prevention of pneumococcal disease. Two currently licensed vaccines have been successful in reducing pneumococcal disease, but there are limitations with their use and effectiveness. Another approach for prevention is the use of live attenuated vaccines. Here we investigate the safety and protection induced by live attenuated strains of S. pneumoniae containing combinations of deletions in genes encoding three of its major virulence determinants: capsular polysaccharide (cps), pneumolysin (ply), and pneumococcal surface protein A (pspA). Both the cps and ply/pspA mutants of a virulent type 6A isolate were significantly attenuated in a mouse model of sepsis. These attenuated strains retained the ability to colonize the upper respiratory tract. A single intranasal administration of live attenuated vaccine without adjuvant was sufficient to induce both systemic and mucosal protection from challenge with a high dose of the parent strain. Immunization with cps mutants demonstrated cross-protective immunity following challenge with a distantly related isolate. Serum and mucosal antibody titers were significantly increased in mice immunized with the vaccine strains, and this antibody is required for full protection, as MT mice, which do not make functional, specific antibody, were not protected by immunization with vaccine strains. Thus, colonization by live attenuated S. pneumoniae is a potentially safe and less complex vaccine strategy that may offer broad protection.

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Immunization with Recombinant Streptococcus pneumoniae Neuraminidase NanA Protects Chinchillas against Nasopharyngeal Colonization

Cited by 33 publications

References 32 publications

The NanA Neuraminidase of Streptococcus pneumoniae Is Involved in Biofilm Formation

The NanA Neuraminidase of Streptococcus pneumoniae Is Involved in Biofilm Formation

An Orthologue of Bacteroides fragilis NanH Is the Principal Sialidase in Tannerella forsythia

Live Attenuated Streptococcus pneumoniae Strains Induce Serotype-Independent Mucosal and Systemic Protection in Mice

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