Moraxella catarrhalis is acknowledged as an important cause of otitis media in infants and very young children and can also cause exacerbations of chronic obstructive pulmonary disease in adults. Little is known about the gene products that allow M. catarrhalis to colonize the nasopharyngeal mucosa and then cause disease in the respiratory tract. The ability of this organism to colonize the mucosal surface of the nasopharynx is crucial to its ability to cause disease in other anatomic regions because this colonization event provides a foothold for M. catarrhalis in its human host. It has been shown that M. catarrhalis forms a biofilm in vivo. We have now identified two different surface proteins (UspA1 and Hag) that form projections on the surface of this bacterium and which are involved in biofilm development. In the first Specific Aim, we will perform structure-function analysis to identify the specific regions of the UspA1 and Hag proteins that are essential for biofilm development. In the second Specific Aim, we will identify those M. catarrhalis surface proteins that are induced or up-regulated when this organism attaches to human cells or when this organism grows in vivo. In the third Specific Aim, we will use mutant analysis together with a chinchilla model of nasopharyngeal colonization by M. catarrhalis to determine which of these surface-exposed proteins of this organism are essential for nasopharyngeal colonization. Finally, in the fourth Specific Aim, we will use this chinchilla model to determine which of these surface proteins can induce the synthesis of antibodies which inhibit or prevent nasopharyngeal colonization by M. catarrhalis. Information gained from this study will directly benefit efforts to develop an effective vaccine to prevent respiratory tract disease caused by M. catarrhalis

Public Health Relevance

Moraxella catarrhalis is a bacterial pathogen that is an important cause of ear infections in babies and serious respiratory tract disease in adults with certain preexisting problems (i.e., chronic obstructive pulmonary disease). Information obtained from this research will identify components of this bacterium that have the potential to be developed into a vaccine to protect against M. catarrhalis disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI036344-15
Application #
8391259
Study Section
Special Emphasis Panel (ZRG1-IDM-H (02))
Program Officer
Taylor, Christopher E,
Project Start
1996-07-01
Project End
2014-11-30
Budget Start
2012-12-01
Budget End
2014-11-30
Support Year
15
Fiscal Year
2013
Total Cost
$325,448
Indirect Cost
$118,156
Name
University of Texas Sw Medical Center Dallas
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
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