Adherence mechanisms of Moraxella catarrhalis

Summary

Principal Investigator: ERIC LAFONTAINE
Abstract: 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.
Funding Period: 2002-12-01 - 2009-11-30
more information: NIH RePORT

Top Publications

  1. pmc Hag directly mediates the adherence of Moraxella catarrhalis to human middle ear cells
    Brian Bullard
    Department of Medical Microbiology and Immunology, Medical College of Ohio, 3055 Arlington Ave, Health Education Bldg, Rm 267, Toledo, OH 43614, USA
    Infect Immun 73:5127-36. 2005
  2. pmc The Moraxella catarrhalis autotransporter McaP is a conserved surface protein that mediates adherence to human epithelial cells through its N-terminal passenger domain
    Serena L Lipski
    Department of Medical Microbiology and Immunology, University of Toledo Health Sciences Campus, 3055 Arlington Avenue, Toledo, Ohio 43614, USA
    Infect Immun 75:314-24. 2007
  3. pmc Moraxella catarrhalis strain O35E expresses two filamentous hemagglutinin-like proteins that mediate adherence to human epithelial cells
    Rachel Balder
    Department of Infectious Diseases, University of Georgia College of Veterinary Medicine, 220 Riverbend Road, South Building Room 146, Athens, GA 30602, USA
    Infect Immun 75:2765-75. 2007
  4. ncbi The Moraxella catarrhalis outer membrane protein CD contains two distinct domains specifying adherence to human lung cells
    Christine Akimana
    Department of Medical Microbiology and Immunology, University of Toledo Health Sciences Campus, Toledo, OH, USA
    FEMS Microbiol Lett 271:12-9. 2007
  5. pmc Regions important for the adhesin activity of Moraxella catarrhalis Hag
    Brian Bullard
    Department of Medical Microbiology and Immunology, University of Toledo Health Sciences Campus, Toledo, OH 43614, USA
    BMC Microbiol 7:65. 2007
  6. pmc 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
    Eric R Lafontaine
    Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602, USA
    Clin Vaccine Immunol 16:653-9. 2009
  7. pmc Hag mediates adherence of Moraxella catarrhalis to ciliated human airway cells
    Rachel Balder
    Department of Infectious Diseases, University of Georgia College of Veterinary Medicine, Athens, Georgia 30602, USA
    Infect Immun 77:4597-608. 2009

Scientific Experts

  • Brian Bullard
  • Eric R Lafontaine
  • Rachel Balder
  • Christine Akimana
  • Serena L Lipski
  • Timothy F Murphy
  • Lauren E Snipes
  • Lacey Feezel
  • Sanjay Sethi
  • Aimee L Brauer
  • Chi Q Nguyen
  • Thomas M Krunkosky
  • Jennifer M Timpe
  • Serena Lipski
  • Jonathan Hassel
  • R Mark Wooten

Detail Information

Publications7

  1. pmc Hag directly mediates the adherence of Moraxella catarrhalis to human middle ear cells
    Brian Bullard
    Department of Medical Microbiology and Immunology, Medical College of Ohio, 3055 Arlington Ave, Health Education Bldg, Rm 267, Toledo, OH 43614, USA
    Infect Immun 73:5127-36. 2005
    ..coli to A549 monolayers. Our data demonstrate that the involvement of Hag in M. catarrhalis adherence to A549 and HMEE cells is conserved among isolates and that Hag directly mediates binding to HMEE cells...
  2. pmc The Moraxella catarrhalis autotransporter McaP is a conserved surface protein that mediates adherence to human epithelial cells through its N-terminal passenger domain
    Serena L Lipski
    Department of Medical Microbiology and Immunology, University of Toledo Health Sciences Campus, 3055 Arlington Avenue, Toledo, Ohio 43614, USA
    Infect Immun 75:314-24. 2007
    ..catarrhalis to A549 human lung cells by up to 47% and to reduce binding of recombinant E. coli expressing McaP by 98%. These results suggest that McaP should be considered as a potential vaccine antigen...
  3. pmc Moraxella catarrhalis strain O35E expresses two filamentous hemagglutinin-like proteins that mediate adherence to human epithelial cells
    Rachel Balder
    Department of Infectious Diseases, University of Georgia College of Veterinary Medicine, 220 Riverbend Road, South Building Room 146, Athens, GA 30602, USA
    Infect Immun 75:2765-75. 2007
    ..The construction of isogenic mutants in the mhaB1 and mhaB2 genes of strain O35E also suggests that the MhaB proteins play distinct roles in M. catarrhalis adherence...
  4. ncbi The Moraxella catarrhalis outer membrane protein CD contains two distinct domains specifying adherence to human lung cells
    Christine Akimana
    Department of Medical Microbiology and Immunology, University of Toledo Health Sciences Campus, Toledo, OH, USA
    FEMS Microbiol Lett 271:12-9. 2007
    ..catarrhalis autotransporter protein McaP, to express foreign peptides on the surface of recombinant bacteria...
  5. pmc Regions important for the adhesin activity of Moraxella catarrhalis Hag
    Brian Bullard
    Department of Medical Microbiology and Immunology, University of Toledo Health Sciences Campus, Toledo, OH 43614, USA
    BMC Microbiol 7:65. 2007
    ..The Moraxella catarrhalis Hag protein, an Oca autotransporter adhesin, has previously been shown to be important for adherence of this respiratory tract pathogen to human middle ear and A549 lung cells...
  6. pmc 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
    Eric R Lafontaine
    Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602, USA
    Clin Vaccine Immunol 16:653-9. 2009
    ....
  7. pmc Hag mediates adherence of Moraxella catarrhalis to ciliated human airway cells
    Rachel Balder
    Department of Infectious Diseases, University of Georgia College of Veterinary Medicine, Athens, Georgia 30602, USA
    Infect Immun 77:4597-608. 2009
    ..These experiments conclusively demonstrate that the hag gene product is responsible for the previously unidentified tropism of M. catarrhalis for ciliated NHBE cells...