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 #
5R01DC010051-02
Application #
7790700
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
2010-04-01
Budget End
2011-03-31
Support Year
2
Fiscal Year
2010
Total Cost
$311,355
Indirect Cost
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
Pang, Bing; Swords, W Edward (2017) Haemophilus parainfluenzae Strain ATCC 33392 Forms Biofilms In Vitro and during Experimental Otitis Media Infections. Infect Immun 85:
Oliver, Melissa B; Basu Roy, Ankita; Kumar, Ranjit et al. (2017) Streptococcus pneumoniae TIGR4 Phase-Locked Opacity Variants Differ in Virulence Phenotypes. mSphere 2:
Kyd, Jennelle M; Hotomi, Muneki; Kono, Masamitsu et al. (2017) Panel 5: Immunology. Otolaryngol Head Neck Surg 156:S63-S75
Grayson, Kristina M; Blevins, Lance K; Oliver, Melissa B et al. (2017) Activation-dependent modulation of Streptococcus pneumoniae-mediated death in human lymphocytes. Pathog Dis 75:
Wren, John T; Blevins, Lance K; Pang, Bing et al. (2017) Pneumococcal Neuraminidase A (NanA) Promotes Biofilm Formation and Synergizes with Influenza A Virus in Nasal Colonization and Middle Ear Infection. Infect Immun 85:
Reimche, Jennifer L; Kirse, Daniel J; Whigham, Amy S et al. (2017) Resistance of non-typeable Haemophilus influenzae biofilms is independent of biofilm size. Pathog Dis 75:
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
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:
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

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