Third-Generation Cephalosporins in the Treatment of Acute Pneumococcal Otitis Media: An Animal Study

Rm, Rosenfeld; Wj, Doyle; Jd, Swarts; Seroky, James T.; Bp, Pinero

doi:10.1001/archotol.1992.01880010053015

Cited by 29 publications

(16 citation statements)

References 8 publications

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“…This action changes the glycosylation patterns of the host and probably exposes more of the host cell surface, which may reveal surface receptors for possible interaction with pneumococci, contributing to increased adhesion and other processes (82). The precise role of S. pneumoniae neuraminidase in pathogenesis has not been clearly established, but it probably enhances colonization due to its action on glycans (128).…”

Section: Neuraminidasementioning

confidence: 99%

Pneumococcal Virulence Factors: Structure and Function

Jedrzejas

2001

Microbiol Mol Biol Rev

407

354

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The overall goal for this review is to summarize the current body of knowledge about the structure and function of major known antigens of Streptococcus pneumoniae, a major gram-positive bacterial pathogen of humans. This information is then related to the role of these proteins in pneumococcal pathogenesis and in the development of new vaccines and/or other antimicrobial agents. S. pneumoniae is the most common cause of fatal community-acquired pneumonia in the elderly and is also one of the most common causes of middle ear infections and meningitis in children. The present vaccine for the pneumococcus consists of a mixture of 23 different capsular polysaccharides. While this vaccine is very effective in young adults, who are normally at low risk of serious disease, it is only about 60% effective in the elderly. In children younger than 2 years the vaccine is ineffective and is not recommended due to the inability of this age group to mount an antibody response to the pneumococcal polysaccharides. Antimicrobial drugs such as penicillin have diminished the risk from pneumococcal disease. Several pneumococcal proteins including pneumococcal surface proteins A and C, hyaluronate lyase, pneumolysin, autolysin, pneumococcal surface antigen A, choline binding protein A, and two neuraminidase enzymes are being investigated as potential vaccine or drug targets. Essentially all of these antigens have been or are being investigated on a structural level in addition to being characterized biochemically. Recently, three-dimensional structures for hyaluronate lyase and pneumococcal surface antigen A became available from X-ray crystallography determinations. Also, modeling studies based on biophysical measurements provided more information about the structures of pneumolysin and pneumococcal surface protein A. Structural and biochemical studies of these pneumococcal virulence factors have facilitated the development of novel antibiotics or protein antigen-based vaccines as an alternative to polysaccharide-based vaccines for the treatment of pneumococcal disease

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Section: Neuraminidasementioning

confidence: 99%

Pneumococcal Virulence Factors: Structure and Function

Jedrzejas

2001

Microbiol Mol Biol Rev

407

354

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“…ME pressure (MEP) of each chinchilla was measured by means of tympanometry. Normal chinchilla MEP was considered to be between Ϫ60 and ϩ40 daPa (17).…”

Section: Animalsmentioning

confidence: 99%

Evaluation of Phase Variation of Nontypeable Haemophilus influenzae Lipooligosaccharide during Nasopharyngeal Colonization and Development of Otitis Media in the Chinchilla Model

et al. 2000

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Nontypeable Haemophilus influenzae (NTHI) has four loci, lic-1 to lic-3 and lgtC, that generate phase-variable lipooligosaccharide (LOS) structures. lic-1, which is required for the expression of phosphorylcholine (ChoP), is the best characterized and is associated with an enhanced ability of H. influenzae to persist within the nasopharynges of infant rats. Recent data indicate that LOS impacts various aspects of NTHI virulence in the chinchilla model of nasopharyngeal colonization and otitis media (OM). In this study the effects of ChoP expression and the sequences of lic-1 to lic-3 and lgtC of NTHI strain 2019 were evaluated in the chinchilla OM model. Nasopharyngeal colonization data showed that a switch from the ChoP ؊ to the ChoP ؉ phenotype was observed as early as day 3 after intranasal inoculation. Chinchillas colonized by strains with the ChoP Otitis media (OM) or inflammation of the middle ear (ME), in one of its various clinical forms, is one of the most common childhood diseases. Nontypeable Haemophilus influenzae (NTHI) is a major OM pathogen and accounts for 25 to 30% of all cases of this disease. The initial event in the pathogenesis of NTHI OM is the colonization of the host mucosal surface; however, the bacterial factors that contribute to the colonization of the nasopharynx, retrograde ascension of the eustachian tube, and invasion of the ME during the natural progression of the disease are not well characterized. NTHI cells are frequently isolated from the upper respiratory tract, especially the nasopharynges of healthy children, with a reported rate of colonization of approximately 80% (8). Recent data suggested that there is a strong relationship between the frequency of colonization and the incidence of OM in children (5).NTHI lipooligosaccharide (LOS) is a major virulence determinant and may play a role in colonization and invasion of mucosal surfaces in the respiratory tract (3, 16, 23). NTHI LOS is analogous to the lipopolysaccharide (LPS) of enteric gramnegative bacteria in that it contains lipid A linked by 3-deoxy-D-manno-octulosonic acid to a heterogeneous sugar polymer (7). NTHI LOS, however, differs from classic enterobacterial LPS in that it does not contain repeating O-antigen units and is therefore more similar to that derived from Neisseria and Bordetella species (14). Moreover, H. influenzae cells demonstrate a propensity to alter or modulate their surface-expressed antigens including LOS (10, 12). NTHI cells express, on their outer surfaces, a number of LOS core oligosaccharide epitopes, and the expression of these epitopes is subject to frequent, reversible phase variation. Four chromosomal loci, lic-1 to lic-3 and lgtC, which contain long stretches of 4-bp tandem repeats within their 5Ј coding regions, have been reported to generate phase-variable LOS structures (9,11,19). lic-1 functions to add phosphorylcholine (ChoP) to the LOS molecule (22), lic-2 and lgtC are necessary for the expression of , and the effect of variation in lic-3 is unknown. Phase variation may represen...

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“…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).…”

mentioning

confidence: 99%

“…3). Normal chinchilla middle ear pressure was considered to be between Ϫ60 and ϩ40 daPa (13). Both the parent and mutant exhibited declines in middle ear pressure, which peaked by day 3 postinoculation.…”

mentioning

confidence: 99%

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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Third-Generation Cephalosporins in the Treatment of Acute Pneumococcal Otitis Media: An Animal Study

Cited by 29 publications

References 8 publications

Pneumococcal Virulence Factors: Structure and Function

Pneumococcal Virulence Factors: Structure and Function

Evaluation of Phase Variation of Nontypeable Haemophilus influenzae Lipooligosaccharide during 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

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