Long considered a harmless commensal of the human respiratory tract, the gram-negative bacterium Moraxella catarrhalis has recently emerged as a significant cause of infectious diseases. These infections are a significant health problem, medically as well as economically, and addressing these issues is complicated by the fact that little is known about pathogenesis by M. catarrhalis. Our long-term objectives are to study the molecular basis for M. catarrhalis adherence to its human host, and to evaluate the potential of interfering with this adherence as a strategy to reduce the risks of infections. We have already isolated E. coli recombinant clones that gained the ability to bind to human cells by virtue of expressing new M. catarrhalis adhesin genes. Furthermore, we have also isolated fourteen M. catarrhalis transposon mutants that are substantially reduced in their ability to bind to human lung cells.
The Specific Aims of the Proposed Research Plan are: 1. To identify and characterize the genes encoding new M. catarrhalis adhesins for human cells. 2. To evaluate the vaccinogenic potential of these new M. catarrhalis adhesins. 3. To identify M. catarrhalis gene products involved in the expression as well as surface display of adhesins ? We will use recombinant DNA techniques as well as transposon mutagenesis to identify genes that are involved in the binding of M. catarrhalis to human cells. We will determine the nucleotide sequence of candidate genes and characterize their encoded products. We will also use recombinant forms of new M. catarrhalis adhesins to determine whether they elicit the production of biologically relevant antibodies. Our studies will have direct applications in vaccine as well as antimicrobial development. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI051477-01A1
Application #
6572519
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Klein, David L
Project Start
2002-12-01
Project End
2007-11-30
Budget Start
2002-12-01
Budget End
2003-11-30
Support Year
1
Fiscal Year
2003
Total Cost
$210,630
Indirect Cost
Name
University of Toledo
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
807418939
City
Toledo
State
OH
Country
United States
Zip Code
43614
Balder, Rachel; Shaffer, Teresa L; Lafontaine, Eric R (2013) Moraxella catarrhalis uses a twin-arginine translocation system to secrete the ?-lactamase BRO-2. BMC Microbiol 13:140
Shaffer, Teresa L; Balder, Rachel; Buskirk, Sean W et al. (2013) Use of the Chinchilla model to evaluate the vaccinogenic potential of the Moraxella catarrhalis filamentous hemagglutinin-like proteins MhaB1 and MhaB2. PLoS One 8:e67881
Balder, Rachel; Krunkosky, Thomas M; Nguyen, Chi Q et al. (2009) Hag mediates adherence of Moraxella catarrhalis to ciliated human airway cells. Infect Immun 77:4597-608
LaFontaine, Eric R; Snipes, Lauren E; Bullard, Brian et al. (2009) Identification of domains of the Hag/MID surface protein recognized by systemic and mucosal antibodies in adults with chronic obstructive pulmonary disease following clearance of Moraxella catarrhalis. Clin Vaccine Immunol 16:653-9
Bullard, Brian; Lipski, Serena; Lafontaine, Eric R (2007) Regions important for the adhesin activity of Moraxella catarrhalis Hag. BMC Microbiol 7:65
Balder, Rachel; Hassel, Jonathan; Lipski, Serena et al. (2007) Moraxella catarrhalis strain O35E expresses two filamentous hemagglutinin-like proteins that mediate adherence to human epithelial cells. Infect Immun 75:2765-75
Akimana, Christine; Lafontaine, Eric R (2007) The Moraxella catarrhalis outer membrane protein CD contains two distinct domains specifying adherence to human lung cells. FEMS Microbiol Lett 271:12-9
Lipski, Serena L; Akimana, Christine; Timpe, Jennifer M et al. (2007) The Moraxella catarrhalis autotransporter McaP is a conserved surface protein that mediates adherence to human epithelial cells through its N-terminal passenger domain. Infect Immun 75:314-24
Bullard, Brian; Lipski, Serena L; Lafontaine, Eric R (2005) Hag directly mediates the adherence of Moraxella catarrhalis to human middle ear cells. Infect Immun 73:5127-36
Holm, Melissa M; Vanlerberg, Serena L; Foley, Ian M et al. (2004) The Moraxella catarrhalis porin-like outer membrane protein CD is an adhesin for human lung cells. Infect Immun 72:1906-13

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