The utilization of molecular oxygen by aerobes is potentially harmful, since its partial reduction results in the formation of superoxide and hydrogen peroxide (H2O2). These products or reduced forms resulting from their interaction are toxic. Aerobic organisms possess protective mechanisms, such as superoxide dismutase, catalase, and peroxidase, and intracellular reductants. Very little is known about the interactions of the aerobic Neisseria gonorrhoeae with reduced forms of oxygen, either from endogenous or exogenous sources. Of particular interest is that some strains of this aerobic microbe lack superoxide dismutase, once considered essential for aerobic life. Evaluation of the interactions of Neisseria gonorrheae with oxygen is a key to understanding the function of superoxide dismutase and the fate of gonococci in their aerobic hosts. The intent of this proposal is to (1) identify the endogenous mechanisms of N. gonorrhoeae which scavenge toxic forms of reduced oxygen, (2) define the mechanisms by which N. gonorrhoeae generates superoxide or H2O2, and (3) determine the gonococcal lesions caused by superoxide and H2O2 and evaluate endogenous generation of partially reduced oxygen for a role in autolysis, and (4) examine oxygen-related interactions of N. gonorrhoeae and host. Concepts in biochemistry, microbiology and cell biology will be used to construct a defined environment for evaluation of interactions of gonococci, partially reduced oxygen, and compounds found in host tissues and fluids. The approach is principally a biochemical one so that the bases of oxygen-induced damage in recent clinical isolates of N. gonorrhoeae can be assessed. Data obtained will improve in vitro methods for cultivation and maintenance of the autolytic N. gonorrhoeae, aid in understanding how N. gonorrhoeae establishes infection in an aerobic host, and help to evaluate the necessity of superoxide dismutase for aerobic life. Studies regarding the mechanisms by which N. gonorrhoeae survive in an aerobic environment may provide information for control of this microbe causing the most common of the reportable infectious diseases in the United States.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI020850-06
Application #
3130652
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1988-06-01
Project End
1992-05-31
Budget Start
1990-06-01
Budget End
1991-05-31
Support Year
6
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Vassar College
Department
Type
Schools of Arts and Sciences
DUNS #
City
Poughkeepsie
State
NY
Country
United States
Zip Code
12604
Norrod, E P; Browne, S L; Feldweg, A et al. (1993) A dominant sulfhydryl-containing protein in the outer membrane of Neisseria gonorrhoeae. J Bacteriol 175:1173-5