Gonorrhea is a disease of antiquity that has been present within human populations for all recorded history. The sole causative agent of gonorrhea is the gram-negative bacterium, Neisseria gonorrhoeae. This bacterium and its close relatives are only found naturally within humans and it is certain that these organisms have been co-evolving with humans for tens of thousands of years. Due to the long co-existence between this organism and its human host, this bacterium represents a highly evolved pathogen that does not produce any exotoxins or overtly aggressive factors but instead produces much of its damage through the promotion of inflammation.
Neisseria gonorrhoeae causes between 300,000 and 700,000 cases of the sexually transmitted disease gonorrhea in the United States each year and many more cases worldwide. The most serious complication of a genital infection is pelvic inflammatory disease (PID), and if the organism disseminates from the genital tract in disseminated gonococcal disease (DGI), arthritis, meningitis, or endocarditis can occur. There are three major problems that complicate the treatment of gonorrhea. (1) Although antibiotic therapy is effective, the rapid rise of antibiotic resistance has resulted in strains that are refractory to treatment. This has landed this organism on the superbug list of the CDC (2007) and has increased the need for new understanding about the pathogenesis of gonococcal disease. 2) Many patients are asymptomatic, particularly women, and if remain untreated will enhance the possibility of women developing pelvic inflammatory disease and also contribute to the continual spread of the organism through high risk populations and increase the risk of disseminated disease (DGI). (3) Infection does not result in long-term immunity to reinfection. The reasons for the lack of natural immunity are now being explained at the molecular level and are though to result from a combination of antigenic variation and suppression of immune responses.
This project was designed to generate data to aid all investigators working in the fields related to gonococcal pathogenesis and to additionally determine whether particular genetic difference between strains correlate with different disease states.
Collaborators for this project include:
- Hank S. Seifert and Brian LeCuyer - Dept of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL
- P. Frederick Sparling and Christopher Thomas - School of Medicine, Division of Infectious Diseases Research, University of North Carolina, Chapel Hill, NC
- William Shafer - Department of Microbiology and Immunology School of Medicine, Emory University , Atlanta, GA
- Michael A. Apicella and Christopher Steichen - Dept. of Microbiology, University of Iowa, Iowa City, IA
- Peter Rice - Division of of Infectious Diseases and Immunology, Dept of Medicine, University of Massachusetts Medical School, Worchester MA
- William L. H. Whittington - Department of Medicine, University of Washington, Seattle WA
- Robert A. Nicholas and Magnus Unemo - Department of Pharmacology, University of North Carolina, Chapel Hill, NC
This sequencing project was supported by the National Institute of Allergy and Infectious Disease, National Institutes of Health funded Genome Sequencing Center for Infectious Diseases at the Broad Institute.