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; Pang, Bing; Richardson, Stephen et al. (2015) Nonencapsulated Streptococcus pneumoniae causes otitis media during single-species infection and during polymicrobial infection with nontypeable Haemophilus influenzae. Pathog Dis 73:
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 73:1-8
Holder, Robert C; Kirse, Daniel J; Evans, Adele K et al. (2015) Otopathogens Detected in Middle Ear Fluid Obtained during Tympanostomy Tube Insertion: Contrasting Purulent and Non-Purulent Effusions. PLoS One 10:e0128606
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
Blevins, Lance K; Wren, John T; Holbrook, Beth C et al. (2014) Coinfection with Streptococcus pneumoniae negatively modulates the size and composition of the ongoing influenza-specific CD8⁺ T cell response. J Immunol 193:5076-87
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
Swords, W Edward (2012) Nontypeable Haemophilus influenzae biofilms: role in chronic airway infections. Front Cell Infect Microbiol 2:97
Pang, Bing; Hong, Wenzhou; Kock, Nancy D et al. (2012) Dps promotes survival of nontypeable Haemophilus influenzae in biofilm communities in vitro and resistance to clearance in vivo. Front Cell Infect Microbiol 2:58
Holder, Robert C; Kirse, Daniel J; Evans, Adele K et al. (2012) One third of middle ear effusions from children undergoing tympanostomy tube placement had multiple bacterial pathogens. BMC Pediatr 12:87
Swords, W Edward (2012) Quorum signaling and sensing by nontypeable Haemophilus influenzae. Front Cell Infect Microbiol 2:100

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