Abstract

The long term goals of this proposal are to identify the active sites of the enterotoxins and exfoliative toxins of Staphylococcus aureus. The toxin molecules will be genetically altered by site-directed mutagenesis of cloned genes and transformed into selected staphylococcal strains for expression. The altered toxins will be tested in animal model systems for loss of biological activity and for the ability to elicit protective antibody. The cat/kitten system will be used to analyze the enterotoxins. Similar studies will be conducted with the exfoliative toxins and the new-born mouse model will be used for assay of biological activity. We will also examine various regions of both toxin types for major immunological epitopes and for mitogenic activity. Mitogenic activity will be assayed by lymphoblast transformation and immunogenicity will be assayed by conventional immunochemical methodology. Regions selected for mutagenesis will be chosen initially on the basis conserved sequence between the serologically diverse molecules. We also intend to characterize and study the mechanism of transmission of a potentially unique class of transposon elements that carry antibiotic resistance and enterotoxin genes. Lastly, we wish to study the transmembrane secretion of these toxins by continuing to analyze a number of secretion mutants we have isolated.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
7R37AI017474-17
Application #
2606358
Study Section
Special Emphasis Panel (NSS)
Project Start
1980-12-01
Project End
1999-11-30
Budget Start
1997-06-01
Budget End
1999-11-30
Support Year
17
Fiscal Year
1996
Total Cost
Indirect Cost

  Institution

Name
University of Oklahoma Health Sciences Center
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
937727907
City
Oklahoma City
State
OK
Country
United States
Zip Code
73117

  Publications

Monday, S R; Vath, G M; Ferens, W A et al. (1999) Unique superantigen activity of staphylococcal exfoliative toxins. J Immunol 162:4550-9
Vath, G M; Earhart, C A; Monie, D D et al. (1999) The crystal structure of exfoliative toxin B: a superantigen with enzymatic activity. Biochemistry 38:10239-46
Crupper, S S; Worrell, V; Stewart, G C et al. (1999) Cloning and expression of cadD, a new cadmium resistance gene of Staphylococcus aureus. J Bacteriol 181:4071-5
McNamara, P J; Iandolo, J J (1998) Genetic instability of the global regulator agr explains the phenotype of the xpr mutation in Staphylococcus aureus KSI9051. J Bacteriol 180:2609-15
Zhang, S; Iandolo, J J; Stewart, G C (1998) The enterotoxin D plasmid of Staphylococcus aureus encodes a second enterotoxin determinant (sej). FEMS Microbiol Lett 168:227-33
Crupper, S S; Gies, A J; Iandolo, J J (1997) Purification and characterization of staphylococcin BacR1, a broad-spectrum bacteriocin. Appl Environ Microbiol 63:4185-90
Crupper, S S; Iandolo, J J (1997) Exploiting the unique biophysical properties of bacteriocins to purify Bac 1829 from Staphylococcus aureus KSI1829. Protein Expr Purif 9:228-32
Crupper, S S; Iandolo, J J (1996) Purification and partial characterization of a novel antibacterial agent (Bac1829) Produced by Staphylococcus aureus KSI1829. Appl Environ Microbiol 62:3171-5
Beharka, A A; Iandolo, J J; Chapes, S K (1995) Staphylococcal enterotoxins bind H-2Db molecules on macrophages. Proc Natl Acad Sci U S A 92:6294-8
Booth, M C; Atkuri, R V; Nanda, S K et al. (1995) Accessory gene regulator controls Staphylococcus aureus virulence in endophthalmitis. Invest Ophthalmol Vis Sci 36:1828-36

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