Abstract

Acute otitis media results from a complex interplay of host defenses, environmental factors, and virulence characteristics of bacteria. Previous studies suggest that Haemophilus influenzae (Hi), an important cause of acute otitis media in children, possess unique genes important in the pathogenesis of this infection. In this project, we will identify potential virulence factors specific for Hi otitis media. Using a subtractive hybridization technique, we will identify DNA fragments present in Hi otitis media isolates and absent in Hi throat isolates. The subtracted DNA fragments will be cloned, sequenced and used to determine their prevalence among large panels of Hi strains grouped by various epidemiologic parameters. Our large collection of Hi strains will be screened for the otitis media associated genes using a gene detection-based microarray consisting of genomes of the Hi strains and associations among these genes as well as between these genes and epidemiologic factors established.
The Specific Aims of this project are: ? ? 1. Characterize Hi isolated from middle ear effusions of children with acute otitis media and from nasopharyngeal throat specimens of children by biotype, serotype, b-lactamase production and genotype by pulsed field gel electrophoresis. ? ? 2. Identify candidate Hi otitis media associated genes through subtractive hybridization. ? ? 3. Describe associations among candidate Hi otitis media associated genes and between Hi otitis media associated genes and epidemiologic parameters, including site of isolation, geographic location, persistence of nasopharyngeal colonization and ability to be transmitted child to child, using a microarray of Hi genomic DNA from each strain in our collections. ? ? 4. Characterize the Hi otitis media associated genes by size, predicted function, and location in the Hi chromosome. ? ? Identification of unique Hi otitis media virulence factors will facilitate the development of novel approaches to the prevention and treatment of Hi otitis media. ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC005840-03
Application #
6793184
Study Section
Special Emphasis Panel (ZDC1-SRB-A (36))
Program Officer
Watson, Bracie
Project Start
2002-09-20
Project End
2007-08-31
Budget Start
2004-09-01
Budget End
2005-08-31
Support Year
3
Fiscal Year
2004
Total Cost
$373,079
Indirect Cost

  Institution

Name
University of Michigan Ann Arbor
Department
Pediatrics
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109

  Publications

Hariadi, Nurul I; Zhang, Lixin; Patel, Mayuri et al. (2015) Comparative Profile of Heme Acquisition Genes in Disease-Causing and Colonizing Nontypeable Haemophilus influenzae and Haemophilus haemolyticus. J Clin Microbiol 53:2132-7
LaCross, Nathan C; Marrs, Carl F; Gilsdorf, Janet R (2014) Otitis media associated polymorphisms in the hemin receptor HemR of nontypeable Haemophilus influenzae. Infect Genet Evol 26:47-57
Davis, Gregg S; Patel, May; Hammond, James et al. (2014) Prevalence, distribution, and sequence diversity of hmwA among commensal and otitis media non-typeable Haemophilus influenzae. Infect Genet Evol 28:223-32
LaCross, Nathan C; Marrs, Carl F; Gilsdorf, Janet R (2013) Population structure in nontypeable Haemophilus influenzae. Infect Genet Evol 14:125-36
Zhang, Lixin; Patel, Mayuri; Xie, Jingping et al. (2013) Urease operon and urease activity in commensal and disease-causing nontypeable Haemophilus influenzae. J Clin Microbiol 51:653-5
Zhang, Lixin; Xie, Jingping; Patel, Mayuri et al. (2012) Nontypeable Haemophilus influenzae genetic islands associated with chronic pulmonary infection. PLoS One 7:e44730
Davis, Gregg S; Sandstedt, Sara A; Patel, Mayuri et al. (2011) Use of bexB to detect the capsule locus in Haemophilus influenzae. J Clin Microbiol 49:2594-601
Nakamura, Shigeki; Shchepetov, Mikhail; Dalia, Ankur B et al. (2011) Molecular basis of increased serum resistance among pulmonary isolates of non-typeable Haemophilus influenzae. PLoS Pathog 7:e1001247
McCrea, Kirk W; Wang, Myron L; Xie, Jingping et al. (2010) Prevalence of the sodC gene in nontypeable Haemophilus influenzae and Haemophilus haemolyticus by microarray-based hybridization. J Clin Microbiol 48:714-9
Sandstedt, Sara A; Marrs, Carl F; Patel, Mayuri et al. (2010) Prevalence of Haemophilus influenzae type b genetic islands among clinical and commensal H. influenzae and H. haemolyticus isolates. J Clin Microbiol 48:2565-8

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