This project aims to define how polymicrobial infection influences bacterial otitis media. Haemophilus influenzae (Hi), Streptococcus pneumoniae (Sp), and Moraxella catarrhalis (Mcat) are the predominant isolates from patients with OM, and a wealth of evidence indicates that OM often involves combinations of these organisms. We hypothesize that interactions between bacterial species can impact OM disease parameters that include bacterial persistence, resistance to clearance and antibiotic treatment, and the initiation, progression and severity of the host inflammatory response. In order to address this hypothesis we will complete the following Specific Aims:
Specific Aim 1 : To define interactions among bacterial pathogens causing OM.
Specific Aim 2. To ask how different interspecies relationships affect experimental OM.
Specific Aim 3. To evaluate impact of polymicrobial infection on antibiotic resistance.
Specific Aim 4. To establish the incidence of coinfection in patients undergoing tympanostomy. Most of our current knowledge about bacterial pathogenesis is derived from infection studies using pure cultures that may not fully represent how infections occur in actual patients. This proposal presents an opportunity to learn how multiple pathogens inhabiting the same ecological niche influence one another in biofilm communities that are critical to persistent infections.

Public Health Relevance

Otitis media is a major common and costly pediatric illness worldwide, accounting for billions of dollars per year in total economic impact. Otitis media infections are the leading reason for pediatric office visits, new antibiotic prescriptions, and surgical instillation of tympanic drain tubes to relieve chronic and recurrent otitis media is the most commonly performed surgical procedure in the U.S. Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis have long been recognized as the most common bacterial causes of otitis media, and it is now clear that many of these infections involve simultaneous infection with more than one organism. The focus of this application is to understand how these bacterial species interact in the biofilm communities that are a major determinant of bacterial persistence in vivo. Understanding how bacteria form these biofilms will be an important step in learning to better diagnose, prevent, and/or treat chronic infections.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC010051-05
Application #
8441597
Study Section
Clinical Research and Field Studies of Infectious Diseases Study Section (CRFS)
Program Officer
Watson, Bracie
Project Start
2009-04-01
Project End
2014-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
5
Fiscal Year
2013
Total Cost
$286,322
Indirect Cost
$92,861
Name
Wake Forest University Health Sciences
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
Murrah, Kyle A; Turner, Roberta L; Pang, Bing et al. (2015) Replication of type 5 adenovirus promotes middle ear infection by Streptococcus pneumoniae in the chinchilla model of otitis media. Pathog Dis 73:8-Jan
Wren, John T; Blevins, Lance K; Pang, Bing et al. (2014) Influenza A virus alters pneumococcal nasal colonization and middle ear infection independently of phase variation. Infect Immun 82:4802-12
Perez, Antonia C; Pang, Bing; King, Lauren B et al. (2014) Residence of Streptococcus pneumoniae and Moraxella catarrhalis within polymicrobial biofilm promotes antibiotic resistance and bacterial persistence in vivo. Pathog Dis 70:280-8
Weimer, Kristin E D; Juneau, Richard A; Murrah, Kyle A et al. (2011) Divergent mechanisms for passive pneumococcal resistance to ýý-lactam antibiotics in the presence of Haemophilus influenzae. J Infect Dis 203:549-55
Juneau, Richard A; Pang, Bing; Weimer, Kristin E D et al. (2011) Nontypeable Haemophilus influenzae initiates formation of neutrophil extracellular traps. Infect Immun 79:431-8
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Weimer, Kristin E D; Armbruster, Chelsie E; Juneau, Richard A et al. (2010) Coinfection with Haemophilus influenzae promotes pneumococcal biofilm formation during experimental otitis media and impedes the progression of pneumococcal disease. J Infect Dis 202:1068-75
Armbruster, Chelsie E; Hong, Wenzhou; Pang, Bing et al. (2009) LuxS promotes biofilm maturation and persistence of nontypeable haemophilus influenzae in vivo via modulation of lipooligosaccharides on the bacterial surface. Infect Immun 77:4081-91