This project aims to define how Moraxella catarrhalis (Mcat) senses quorum signals produced by other organisms. Mcat is among are the predominant agents causing otitis media and other opportunistic airway infections, and our data show that Mcat can sense dihydroxypentanedione (DPD) quorum signals produced by Haemophilus influenzae. We hypothesize that Mcat "eavesdrops" on quorum signal molecules produced by other pathogens, resulting in increased production of the Hag adhesin and concomitant increases in biofilm resistance properties. In order to address this hypothesis we will complete the following Specific Aims:
Specific Aim 1 : To identify determinants of DPD uptake by Mcat.
Specific Aim 2. To define the determinants of DPD response in Mcat.
Specific Aim 3. To define importance of quorum signal eavesdropping in Mcat persistence and virulence during experimental otitis media. Otitis media is among the most common pediatric infectious diseases, affecting the majority of children and accounting for billions of dollars in total health care costs per year. It is clear that a significant proportion of these infections are caused by Mcat, for which there is no currently licensed vaccine. Unfortunately, our ability to treat these infections is increasingly limited by the continued emergence of antibiotic-resistant bacterial strains. The results of these studies will provide significant insight into mechanisms for the persistence of Mcat in the polymicrobial infections that represent the majority of cases. Such insights could be pivotal advances in the design of new means for treatment of chronic Mcat 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. and it is clear that Moraxella catarrhalis is a major cause of these infections. It is thus of great importance to improve our knowledge of M. catarrhalis biology and pathogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC012205-02
Application #
8423001
Study Section
Clinical Research and Field Studies of Infectious Diseases Study Section (CRFS)
Program Officer
Watson, Bracie
Project Start
2012-02-07
Project End
2017-01-31
Budget Start
2013-02-01
Budget End
2014-01-31
Support Year
2
Fiscal Year
2013
Total Cost
$298,775
Indirect Cost
$96,900
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