Non-encapsulated Haemophilus influenzae are frequently isolated from the sputum of patients with chronic bronchitis but the role of these organisms in the pathogenicity of this disease is poorly understood. The purpose of this proposal is to study the macromolecular and ultrastructural characteristics of a wide range of non-encapsulated H. influenzae to attempt to identify cell wall constituents which may be associated with virulence. This will be accomplished through the following specific aims: 1) outer membrane protein patterns of 200 strains of non-encapsulated H. influenzae will be determined by SDS-PAGE and an appropriate serotype system established. 2) A lipopolysaccharide serotyping system will be established initially using alkaline digested LPS isolated from 25 H. influenzae strains and antisera made to these strains. After specific LPS types are identified the remaining 175 strains will be screened by IFA. Strains which fail to type will be studied for potentially new serotypes. 3) One hundred strains of non-encapsulated H. influenzae freshly isolated from sputa will be studied by transmission electron microscopy after negative straining for the presence of pili. 4) An organ culture model will be established using both hamster tracheal rings and human bronchial tissue obtained at surgery. These models wil be studied; a) with representative strains of each outer membrane and LPS serotype to determine if differences in adherence and invasion can be observed. b) to determine if piliation enhances attachment and if non-piliated strains can attach to the organ culture model. c) to determine whether previously diseased bronchial tissue is more susceptible to H. influenzae attachment and invasion than normal tissue. d) to determine if prior infection of the hamspter tracheal model with mycoplasms or influenzae virus enhances attachment and invasion by H. influenzae. e) to determine if pathologic changes induced in the bronchial organ culture model by viable organisms can be induced by outer membrane proteins and lipopolysaccharide isolated from these strains. f) to determine if monoclonal antibody to the H. influenzae cell surface constituents can prevent attachment, invasion and toxicity after infection in the tracheal organ culture model.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI019641-03
Application #
3128982
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1983-09-30
Project End
1986-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
State University of New York at Buffalo
Department
Type
Schools of Medicine
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260
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Jacobs, David M; Ochs-Balcom, Heather M; Zhao, Jiwei et al. (2018) Lower Airway Bacterial Colonization Patterns and Species-Specific Interactions in Chronic Obstructive Pulmonary Disease. J Clin Microbiol 56:
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Pettigrew, Melinda M; Alderson, Mark R; Bakaletz, Lauren O et al. (2017) Panel 6: Vaccines. Otolaryngol Head Neck Surg 156:S76-S87
Murphy, Timothy F; Kirkham, Charmaine; Gallo, Mary C et al. (2017) Immunoglobulin A Protease Variants Facilitate Intracellular Survival in Epithelial Cells By Nontypeable Haemophilus influenzae That Persist in the Human Respiratory Tract in Chronic Obstructive Pulmonary Disease. J Infect Dis 216:1295-1302
Post, Deborah M B; Ketterer, Margaret R; Coffin, Jeremy E et al. (2016) Comparative Analyses of the Lipooligosaccharides from Nontypeable Haemophilus influenzae and Haemophilus haemolyticus Show Differences in Sialic Acid and Phosphorylcholine Modifications. Infect Immun 84:765-74
Hu, Fang; Rishishwar, Lavanya; Sivadas, Ambily et al. (2016) Comparative Genomic Analysis of Haemophilus haemolyticus and Nontypeable Haemophilus influenzae and a New Testing Scheme for Their Discrimination. J Clin Microbiol 54:3010-3017

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