Francis J. Castellino

Francis J. Castellino

University of Notre Dame, USA

Title: The evolution of virulence in Streptococcus pyogenes


2006-present Adjunct Professor of Biochemistry & Molecular Biology, Indiana University School of Medicine 1996-present Director, WM Keck Center for Transgene Research, University of Notre Dame 1983-present Kleiderer/Pezold Professor of Biochemistry, University of Notre Dame 1979-2002 Dean, College of Science, University of Notre Dame 1977-1983 Professor, University of Notre Dame 1974-1977 Associate Professor, University of Notre Dame 1970-1974 Assistant Professor, University of Notre Dame 1968-1970 NIH Postdoctoral Fellow, Duke University 1968 Ph.D. in Biochemistry, University of Iowa 1964 B.S. University of Scranton


The virulence determinants of Gram-positive streptococci are more complex than those of Gram-negative strains. For Gram-negative bacteria, lipopolysaccharide (LPS) is a primary virulence factor. In the case of the human pathogen, Gram-positive group A-streptococcus pyogenes (GAS), several factors play various roles as virulence determinants. These include cell wall components, lipoteichoic acidand peptidoglycan, along with the cell wall capsule and exotoxins, from both the bacterial genome, e.g., the cysteine protease, streptococcal pyrogenic exotoxin (Spe)B, and from bacteriophage inserts, e.g.,the DNase, streptodornase I (SdaI) and the superantigen, SpeA. Genes are also acquired by GAS strains via horizontal transfer, e.g.,emm, enn, and fcR genes, as well as streptokinase (the ska gene), which functions in virulence through activation of host human plasminogen. The products of these genes attempt to defeat both innate and acquired immunity of the host.These virulence factors are under control of one-component and two-component bacterial regulatory systems, which regulate gene expression as needed at different stages during infection. Thistalk will detail the functions of bacterial virulence determinants and their dynamic interplay with the innate and acquired immune system of the host.