Neisseria gonorrhoeae is responsible for over 1 million cases of gonorrhea each year in the United States and the total health care costs associated with treating gonorrhea, and complications that arise from infections caused by this organism exceed 1 billion dollars per year. An effective vaccine would dramatically reduce the associated health care costs. This proposal focuses on elucidating the genetic mechanisms responsible for the expression of one of the organism's principal surface antigens, lipooligosaccharide (LOS). In the work to be described, I will identify by gene cloning and genetic complementation techniques, genes required for the LOS biosynthesis. I will characterize these genes by DNA sequence analysis, define the biochemical properties of the gene products and determine their role in the biosynthetic process. Since the gonococcus can vary its LOS, depending on the host and the local environment, studies on the genetic regulation of its synthesis are warranted. Stable LOS-producing strains are needed to allow us to dissect the role of LOS in the disease process. I will construct a series of genetically defined LOS mutants that express defined LOS structures. These strains will also allow us to study the interaction of the expression of this molecule with other cell surface components. Understanding how the expression of LOS is regulated will allow us to design experiments to test the role of each cell surface component in the disease process. By understanding the relationship between disease and the expression of a specific surface component, we can design vaccines that can prevent the disease in specific demographic groups.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI024452-10A2
Application #
6194685
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Quackenbush, Robert L
Project Start
1988-09-30
Project End
2005-05-31
Budget Start
2000-06-01
Budget End
2001-05-31
Support Year
10
Fiscal Year
2000
Total Cost
$259,000
Indirect Cost
Name
University of Maryland College Park
Department
Anatomy/Cell Biology
Type
Schools of Earth Sciences/Natur
DUNS #
City
College Park
State
MD
Country
United States
Zip Code
20742
Edwards, Vonetta L; Wang, Liang-Chun; Dawson, Valerie et al. (2013) Neisseria gonorrhoeae breaches the apical junction of polarized epithelial cells for transmigration by activating EGFR. Cell Microbiol 15:1042-57
LeVan, Adriana; Zimmerman, Lindsey I; Mahle, Amanda C et al. (2012) Construction and characterization of a derivative of Neisseria gonorrhoeae strain MS11 devoid of all opa genes. J Bacteriol 194:6468-78
John, Constance M; Liu, Mingfeng; Phillips, Nancy J et al. (2012) Lack of lipid A pyrophosphorylation and functional lptA reduces inflammation by Neisseria commensals. Infect Immun 80:4014-26
Swanson, Karen V; Griffiss, J McLeod; Edwards, Vonetta L et al. (2011) Neisseria gonorrhoeae-induced transactivation of EGFR enhances gonococcal invasion. Cell Microbiol 13:1078-90
Stein, Daniel C; Miller, Clinton J; Bhoopalan, Senthil V et al. (2011) Sequence-based predictions of lipooligosaccharide diversity in the Neisseriaceae and their implication in pathogenicity. PLoS One 6:e18923
Kwiatek, Agnieszka; Luczkiewicz, Maciej; Bandyra, Katarzyna et al. (2010) Neisseria gonorrhoeae FA1090 carries genes encoding two classes of Vsr endonucleases. J Bacteriol 192:3951-60
Stein, Daniel C; Carrizosa, Esteban; Dunham, Stephen (2009) Use of nfsB, encoding nitroreductase, as a reporter gene to determine the mutational spectrum of spontaneous mutations in Neisseria gonorrhoeae. BMC Microbiol 9:239
O'Connor, Ellen T; Zhou, Hui; Bullock, Kevin et al. (2009) Structural characterization of an oligosaccharide made by Neisseria sicca. J Bacteriol 191:3311-20
Bish, Samuel E; Song, Wenxia; Stein, Daniel C (2008) Quantification of bacterial internalization by host cells using a beta-lactamase reporter strain: Neisseria gonorrhoeae invasion into cervical epithelial cells requires bacterial viability. Microbes Infect 10:1182-91