Abstract

The PI proposes studies of the structure, function and genetics of the gonococcal lactoferrin (LF) receptor. Principal questions include the frequency of expression in fresh clinical isolates of the two proteins (LbpB and LbpA) that make up the receptor. We will address whether gonococci expressing the LF receptor are better equipped to attach to eukaryotic cells, and to cause urethral infection in human volunteers. The protein domains in LbpB and LbpA that bind LF will be analyzed, as will the functional contribution of LbpB to the various functions of the LF receptor. We will test whether there is high frequency variation in expression of LbpB, and the genetic basis for frequent deletions in lbpb and lbpa. Antibodies will be raised against LbpB and LbpA to assess the potential of these antigens as components of a vaccine for gonorrhea, and to assist in studies of structure and function of the proteins. The studies are important for better understanding gonococcal pathogenesis and vaccine development, and also other mucosal pathogens including meningococci that infect similar mucosal surfaces and that make comparable receptors.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI026837-13
Application #
6373146
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Quackenbush, Robert L
Project Start
1988-07-01
Project End
2004-03-31
Budget Start
2001-04-01
Budget End
2002-03-31
Support Year
13
Fiscal Year
2001
Total Cost
$360,121
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

Thomas, Christopher E; Zhu, Weiyan; Van Dam, Cornelius N et al. (2006) Vaccination of mice with gonococcal TbpB expressed in vivo from Venezuelan equine encephalitis viral replicon particles. Infect Immun 74:1612-20
Zhu, Weiyan; Thomas, Christopher E; Chen, Ching-Ju et al. (2005) Comparison of immune responses to gonococcal PorB delivered as outer membrane vesicles, recombinant protein, or Venezuelan equine encephalitis virus replicon particles. Infect Immun 73:7558-68
Zhu, W; Thomas, C E; Sparling, P F (2004) DNA immunization of mice with a plasmid encoding Neisseria gonorrhea PorB protein by intramuscular injection and epidermal particle bombardment. Vaccine 22:660-9
Anderson, James E; Hobbs, Marcia M; Biswas, Gour D et al. (2003) Opposing selective forces for expression of the gonococcal lactoferrin receptor. Mol Microbiol 48:1325-37
Chen, Ching-Ju; Mclean, Dalton; Thomas, Christopher E et al. (2002) Point mutations in HpuB enable gonococcal HpuA deletion mutants to grow on hemoglobin. J Bacteriol 184:420-6
Turner, P C; Thomas, C E; Stojiljkovic, I et al. (2001) Neisserial TonB-dependent outer-membrane proteins: detection, regulation and distribution of three putative candidates identified from the genome sequences. Microbiology 147:1277-90
Cornelissen, C N; Anderson, J E; Boulton, I C et al. (2000) Antigenic and sequence diversity in gonococcal transferrin-binding protein A. Infect Immun 68:4725-35
Biswas, G D; Anderson, J E; Chen, C J et al. (1999) Identification and functional characterization of the Neisseria gonorrhoeae lbpB gene product. Infect Immun 67:455-9
Chen, C J; Elkins, C; Sparling, P F (1998) Phase variation of hemoglobin utilization in Neisseria gonorrhoeae. Infect Immun 66:987-93
Turner, P C; Thomas, C E; Elkins, C et al. (1998) Neisseria gonorrhoeae heme biosynthetic mutants utilize heme and hemoglobin as a heme source but fail to grow within epithelial cells. Infect Immun 66:5215-23

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