Joseph J Ferretti, PhD

 

Professor

Ph.D.: 1967, University of Minnesota

Pre-OUHSC: Johns Hopkins University

Research Interests: Molecular biology of streptococcal virulence factors; mechanisms of phage conversion; protein engineering and second generation streptokinases; synthetic vaccines and passive immunization.

Teaching: Past George Lynn Cross Research Professor and Head Molecular Biology of Streptococcal Virulence

Email: Joseph-Ferretti@ouhsc.edu



Research Emphasis

As a group of organisms, the streptococci are responsible for a wide variety of human diseases, including throat and skin infections, rheumatic fever, glomerulonephritis, and dental caries. In this laboratory, the genetics and molecular biology of two specific organisms are being studied; the pyogenic Streptococcus pyogenes, and the cariogenic Streptococcus mutans.

Dr. Ferretti's research has focused on obtaining individual genes by recombinant DNA techniques in order to study their role in pathogenesis and virulence. Additionally, these genes can be useful as DNA probes for identification, detection, and molecular epidemiology, as well as for the production of medically important proteins. The extracellular products of S. pyogenes have long been implicated in the virulence and pathogenicity of the organism.

To date, a number of the genes specifying these products have been cloned and sequenced, including streptokinase, streptolysin O, erythrogenic toxin A, hyaluronidase, and proteinase. The recent application of electroporation to these bacteria has allowed the construction of isogenic strains with deletions in one or more of the above listed genes. These isogenic mutant strains are of particular interest in animal model studies in assessing the role of each product in the disease state.

 

Dental caries are caused by oral streptococci and Dr. Ferretti's laboratory has cloned and sequenced a number of genes involved in extracellular glucan production and adherence, factors intimately associated with the ability of these organisms to cause caries. These genes include glucosyltransferases S and I, glucan binding protein, wall associated protein antigen A, and a number of genes involved in sucrose metabolism.

Several of the proteins specified by these genes have been shown to be effective as candidate antigens for a caries vaccine. Work is presently underway to identify protein domains particularly important for function or antigenicity, factors that are important for designing specific inhibitors or synthetic vaccines.

The genetics of sugar transport and metabolism by Streptococcus mutans are also areas of interest in this laboratory. The description of extracellular and intracellular components or pathways involved in sugar metabolism is essential to our understanding of the virulence of this organism. Recent work has centered on regulatory mechanisms of the multiple sugar metabolism, galactose, and glucose facilitated diffusion operons.


Selected Publications:

Russell, R.R.B., J. Aduse-Opuko, I.C. Sutcliffe, L. Tao, and J.J. Ferretti. 1992. A binding protein-dependent transport system in Streptococcus mutans responsible for multiple sugar metabolism. J. Biol. Chem. 267: 4631-4637.

Tao, L., D.J. LeBlanc and J.J. Ferretti. 1992. Novel streptococcal-integration shuttle vectors for gene cloning and inactivation. Gene 120: 105-110.

Gilmore, K.S., R.R.B. Russell and J.J. Ferretti. 1993. Expression of gtfS is essential for normal insoluble glucan synthesis by Streptococcus downeiInfect. Immun. 61: 1246-1250.

Chaussee, M., D. Gerlach, C.E. Yu, and J.J. Ferretti. 1993. Inactivations of the streptococcal erythrogenic toxin B (speB) gene in Streptococcus pyogenesInfect. Immun. 61: 3719-3723.

Hynes, W.L., J.J. Ferretti, and J.R. Tagg. 1993. Cloning of the gene encoding streptococcin A-FF22, a novel lantibiotic produced by Streptococcus pyogenes, and determination of its nucleotide sequence. Appl. Environ. Microbiol. 59: 1969-71.