The overall goal of this research is to study the determinants of virulence in beta hemolytic streptococci. The techniques of recombinant DNA technology have allowed new approaches to be taken in the study of these pathogenic orgnaisms. Specifically, the multifactorial properties of the organism thought to be responsible for the disease state can now be individually isolated and subjected to intense study at the molcular level. We have isolated several genes from hemolytic streptococci which produce extracellular products known to be involved in the initiation of tissue damage; i.e., erythrogenic toxin, proteinase, streptokinase, hyaluronidase, and streptolysin O. The specific amis of this investgation are to: 1. Utilize DNA probes from the above extracellular product genes in hybridization experiments to determine the presence of these genes in a large number of streptococcal strains obtained throughout the world, and to determine whether individual determinants can be linked to strains associated with a specific disease; e.g., acute glomerulonephrintis, rheumatic fever, or scarlet fever. 2. Elucidate the study further the mechanism of toxigenic conversion by whihc lysogenic strains of S. poygenes produce the type A erythrogenic toxin. 3. Determine whether the type B erythrogenic toxin and the zymogen precursor of streptococcal proteinase are the same products, and study the determinants of these products at the molecular level. 4. Perform site directed mutagenesis and protein engineering experiments with the cloned streptokinase gene in order to study structure function relationships of this protein and also obtain second generation streptokinases. Additionally, study in further detail the group A streptokinase, which has recently been identified as te nephritis strain-associated antigen. These studies should provide information about structure function relationships of individual gene products, how they regulated, their distriubtion among streptococci and related organisms, and further insight into mechanisms of action and role in pathogenesis. Specific DNA probes will also be available for developing reapid detection and identification systems, as well as the linking of particular determinants to streptococcal strains associated with specific diseases. Finally, second generation streptokinases will be constructed which could have immediate clinical applicability in thrombolytic therapy.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Oklahoma Health Sciences Center
School of Medicine & Dentistry
Oklahoma City
United States
Zip Code
Ferretti, Joseph J; Ajdic, Dragana; McShan, W Michael (2004) Comparative genomics of streptococcal species. Indian J Med Res 119 Suppl:1-6
Suvorov, Alexander N; Ferretti, Joseph J (2004) Construction of a GBS-GAS DNA subtraction library allows discovery of previously unidentified GBS genes and rapid location of unique regions on the GBS chromosome. J Basic Microbiol 44:66-74
Savic, Dragutin J; McShan, William M; Ferretti, Joseph J (2002) Autonomous expression of the slo gene of the bicistronic nga-slo operon of Streptococcus pyogenes. Infect Immun 70:2730-3
Dmitriev, A; Hu, Y Y; Shen, A D et al. (2002) Chromosomal analysis of group B streptococcal clinical strains; bac gene-positive strains are genetically homogenous. FEMS Microbiol Lett 208:93-8
Dmitriev, A; Shakleina, E; Tkacikova, L et al. (2002) Genetic heterogeneity of the pathogenic potentials of human and bovine group B streptococci. Folia Microbiol (Praha) 47:291-5
Koroleva, Irina V; Efstratiou, Androulla; Suvorov, Alexander N (2002) Structural heterogeneity of the streptococcal C5a peptidase gene in Streptococcus pyogenes. J Bacteriol 184:6384-6
Suvorov, A N; Ferretti, J J (2000) Replication origin of Streptococcus pyogenes, organization and cloning in heterologous systems. FEMS Microbiol Lett 189:293-7
Gase, K; Ferretti, J J; Primeaux, C et al. (1999) Identification, cloning, and expression of the CAMP factor gene (cfa) of group A streptococci. Infect Immun 67:4725-31
McShan, W M; Ferretti, J J (1997) Genetic diversity in temperate bacteriophages of Streptococcus pyogenes: identification of a second attachment site for phages carrying the erythrogenic toxin A gene. J Bacteriol 179:6509-11
Chaussee, M S; Phillips, E R; Ferretti, J J (1997) Temporal production of streptococcal erythrogenic toxin B (streptococcal cysteine proteinase) in response to nutrient depletion. Infect Immun 65:1956-9

Showing the most recent 10 out of 27 publications