This application is for competitive renewal of an R01 project focused on defining determinants of bacterial persistence in biofilms during otitis media infections. Otitis media is caused by airway opportunists such as Haemophilus influenzae (Hi, which forms biofilm communities that promote bacterial persistence within the middle-ear chamber. During the first four years of support we have defined mechanism(s) involved in biofilm formation by Hi, and proved that biofilms promote bacterial persistence in vivo. For the next project period we will define determinants of biofilm resistance to host clearance. We hypothesize that biofilms promote bacterial resistance to clearance because of activation of bacterial stress-responses within the biofilm, and inherent resistance to host phagocytes. In order to address these hypotheses we will complete the following Specific Aims:
Specific Aim 1 : To delineate role(s) of bacterial stress-responses in Hi persistence during experimental otitis media.
Specific Aim 2 : To define resistance of Hi biofilms to phagocytic and extracellular killing. Although it is clear that the biofilm mode of growth is involved in the majority of persistent infections, much remains to be learned about the determinants of bacterial resistance to clearance within biofilms. The completion of the proposed work will enhance our understanding of the role of biofilms within the clinical context of otitis media.

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 has long been recognized as the most common bacterial causes of otitis media, and it is now clear that H. influenzae forms biofilms that are important determinants of persistent infections. The focus of this application is to understand how these biofilm communities promote 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 #
5R01DC007444-07
Application #
8092811
Study Section
Clinical Research and Field Studies of Infectious Diseases Study Section (CRFS)
Program Officer
Watson, Bracie
Project Start
2005-04-01
Project End
2015-05-31
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
7
Fiscal Year
2011
Total Cost
$304,436
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
Juneau, Richard A; Pang, Bing; Armbruster, Chelsie E et al. (2015) Peroxiredoxin-glutaredoxin and catalase promote resistance of nontypeable Haemophilus influenzae 86-028NP to oxidants and survival within neutrophil extracellular traps. Infect Immun 83:239-46
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
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:
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
Swords, W Edward (2012) Quorum signaling and sensing by nontypeable Haemophilus influenzae. Front Cell Infect Microbiol 2:100

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