Otitis media (middle ear inflammation) ranks first among the most common diagnoses requiring a physician's office visit and recent estimates indicate that virtually all children (99%) will experience a least one episode of otitis media (OM) by age 2. The disease progresses in many children to recurrent infections and chronic inflammation, often with complications and sequalae that include persistent hearing loss nd communication disorders. Streptococcus pneumoniae (Spn), is one of the foremost human pathogens and is the primary nasopharynx, the initial event in the induction of OM and the mechanisms which effect the transition for a colonized state to invasion of the middle ear and the induction of the disease state by Spn are not known. The long term objectives of this proposal are to delineate the pathogenic mechanisms involved in Spn adherence, colonization, and invasion of the middle ear and to develop a scientific rationale for the design of novel diagnostic and prevention strategies.
The specific aims of this proposal are: 1) To continue to define the role of Spn neuraminidase in the pathogenesis of OM and to assess whether it is a protective antigen and a potential protein-based vaccine candidate, and whether neuraminidase inhibitors are effective in the prevention of Spn nasopharyngeal colonization of OM. 2) To assess the efficacy of lacto-N-neotetraose, a Spn carbohydrate receptor analog, as an anti-infective for nasopharyngeal colonization. 3) To continue to define the mechanisms whereby influenza A virus affects Spn adherence, colonization, and OM.
These aims are designed to delineate the initial interaction, adherence, and colonization which represents the first in a series of steps that culminates in otitis media. These studies may suggest avenues for blocking interaction of Spn with host cells either by immunization or direct intervention blockade with isolated receptor moieties or bacterial adhesin components.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC003105-07
Application #
6523439
Study Section
Special Emphasis Panel (ZRG1-IFCN-6 (01))
Program Officer
Watson, Bracie
Project Start
1996-08-01
Project End
2005-07-31
Budget Start
2002-08-01
Budget End
2003-07-31
Support Year
7
Fiscal Year
2002
Total Cost
$277,300
Indirect Cost
Name
Ohio State University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210
Chen, Shu; Paterson, Gavin K; Tong, Hua Hua et al. (2005) Sortase A contributes to pneumococcal nasopharyngeal colonization in the chinchilla model. FEMS Microbiol Lett 253:151-4
Tong, H H; Li, D; Chen, S et al. (2005) Immunization with recombinant Streptococcus pneumoniae neuraminidase NanA protects chinchillas against nasopharyngeal colonization. Infect Immun 73:7775-8
Long, J P; Tong, H H; DeMaria, T F (2004) Immunization with native or recombinant Streptococcus pneumoniae neuraminidase affords protection in the chinchilla otitis media model. Infect Immun 72:4309-13
Tong, Hua Hua; Long, James P; Li, Daneng et al. (2004) Alteration of gene expression in human middle ear epithelial cells induced by influenza A virus and its implication for the pathogenesis of otitis media. Microb Pathog 37:193-204
Tong, H H; Long, J P; Shannon, P A et al. (2003) Expression of cytokine and chemokine genes by human middle ear epithelial cells induced by influenza A virus and Streptococcus pneumoniae opacity variants. Infect Immun 71:4289-96
Long, J P; Tong, H H; Shannon, P A et al. (2003) Differential expression of cytokine genes and inducible nitric oxide synthase induced by opacity phenotype variants of Streptococcus pneumoniae during acute otitis media in the rat. Infect Immun 71:5531-40
Tong, H H; Grants, I; Liu, X et al. (2002) Comparison of alteration of cell surface carbohydrates of the chinchilla tubotympanum and colonial opacity phenotype of Streptococcus pneumoniae during experimental pneumococcal otitis media with or without an antecedent influenza A virus infection. Infect Immun 70:4292-301
Tong, Hua Hua; Liu, Xia; Chen, Yiping et al. (2002) Effect of neuraminidase on receptor-mediated adherence of Streptococcus pneumoniae to chinchilla tracheal epithelium. Acta Otolaryngol 122:413-9
Tong, H H; Weiser, J N; James, M A et al. (2001) Effect of influenza A virus infection on nasopharyngeal colonization and otitis media induced by transparent or opaque phenotype variants of Streptococcus pneumoniae in the chinchilla model. Infect Immun 69:602-6
Tong, H H; James, M; Grants, I et al. (2001) Comparison of structural changes of cell surface carbohydrates in the eustachian tube epithelium of chinchillas infected with a Streptococcus pneumoniae neuraminidase-deficient mutant or its isogenic parent strain. Microb Pathog 31:309-17

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