: This project aims to define how changes in the composition of Haemophilus influenzae lipooligosaccharides affect biofilms. H. influenzae biofilms cause chronic otitis media infections that are among the most common and costly public health problems in the world. Biofilms formed in the middle ear during otitis media resist pharmaceutical or immune clearance. We recently discovered that the lipooligosaccharide glycolipids in H. influenzae biofilms contain sialic acid and phosphorylcholine that contribute to the progression of otitis in a chinchilla middle-ear infection model system. ? We hypothesize that changes in the composition of H. influenzae lipooligosaccharides promote the formation of mature biofilms, thus increasing resistance to clearance, and decreasing innate responses. To address this hypothesis, we will complete the following Specific Aims: ? Specific Aim 1: To delineate how lipooligosaccharide composition promotes H. influenzae biofilm phenotypes in vitro. Benchmarks for defining mature biofilms include decreased host inflammatory responses, and increased biofilm density and structure that promotes resistance to killing by antibiotics. ? Specific Aim 2: To establish the role of biofilm-related changes in lipooligosaccharides in H. influenzae otitis media. We will use the chinchilla animal model for otitis media to evaluate how changes in lipooligosaccharide composition observed in biofilms in vitro increase H. influenzae persistence and virulence in vivo. ? The completion of these Specific Aims will elucidate biofilm growth mechanisms that are critical to otitis media and other chronic infections. No vaccine in current use protects against the unencapsulated H. influenzae strains that cause otitis, and antibiotic resistance increasingly limits treatment options for these infections. This problem is made even worse by the inherent resistance of biofilms to most antibiotics. A better understanding of biofilms will be crucial to the rational design of new ways to diagnose, treat or prevent chronic otitis media. The research proposed here thus presents an important opportunity to identify new targets for eliminating one of the most costly and prevalent problems in public health worldwide. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
1R01DC007444-01
Application #
6908829
Study Section
Bacterial Pathogenesis Study Section (BACP)
Program Officer
Watson, Bracie
Project Start
2005-04-01
Project End
2010-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
1
Fiscal Year
2005
Total Cost
$287,000
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
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
Pang, Bing; Swords, W Edward (2017) Haemophilus parainfluenzae Strain ATCC 33392 Forms Biofilms In Vitro and during Experimental Otitis Media Infections. Infect Immun 85:
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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